IMmotion151: A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02420821
• Collaborator: (none)
• Enrollment: 915
• Locations: 154
• Arms: 2
• Actual Duration (Months): 78.8
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This multi-center, randomized, open-label study will evaluate the efficacy and safety of atezolizumab plus bevacizumab versus sunitinib in participants with inoperable, locally advanced, or metastatic RCC who have not received prior systemic active or experimental therapy, either in the adjuvant or metastatic setting.

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Carcinoma	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Bevacizumab; Drug: Sunitinib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 915 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Open-Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
• Actual Study Start Date: May 20, 2015
• Actual Primary Completion Date: Sep 29, 2017
• Actual Study Completion Date: Dec 13, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atezolizumab + Bevacizumab Participants will receive both atezolizumab and bevacizumab until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Days 1 and 22 of each 42-day cycle.; Other Names: Tecentriq, MPDL3280A ; Drug: Bevacizumab; Bevacizumab will be administered at a dose of 15 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 22 of each 42-day cycle.; Other Names: Avastin
Active Comparator: Sunitinib Participants will receive sunitinib until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.	Drug: Sunitinib; Sunitinib will be administered at a dose of 50 mg once daily, orally via capsule, on Day 1 through Day 28 of each 42-day cycle.; Other Names: Sutent

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Disease Progression as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death From Any Cause in Programmed Death-Ligand 1 (PD-L1)-Selected Population [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

   Tumor response was assessed by the investigator according to RECIST v1.1. Disease Progression (PD) was defined as greater than or equal to (>/=) 20 percent (%) relative increase in the sum of diameters (SoD) of all target lesions (TLs), taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 millimeters (mm); >/=1 new lesion(s); and/or unequivocal progression of existing non-TLs.

2. Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected Population [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

   PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% confidence interval (CI) was assessed using the method of Brookmeyer and Crowley.

3. Percentage of Participants Who Died of Any Cause in ITT Population [Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)]

   Percentage of participants who died of any cause was reported.

4. Overall Survival (OS) in ITT Population [Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)]

   OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

Secondary Outcome Measures

1. Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population [Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)]

   Percentage of participants who died of any cause was reported.

2. OS in PD-L1-Selected Population [Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)]

   OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

3. Percentage of Participants With PD as Determined by an Independent Review Committee (IRC) According to RECIST v1.1 or Death From Any Cause in ITT Population [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

   Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.

4. PFS as Determined by an IRC According to RECIST v1.1 in ITT Population [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

   PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

5. Percentage of Participants With PD as Determined by an IRC According to RECIST v1.1 or Death From Any Cause in PD-L1-Selected Population [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

   Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.

6. PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected Population [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

   PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

7. Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator According to RECIST v1.1 in Objective Response Rate (ORR)-Evaluable Population [Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

   Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to less than (<) 10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.

8. Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable Population [Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

   DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.

9. Percentage of Participants With an Objective Response of CR or PR as Determined by an IRC According to RECIST v1.1 in ORR-Evaluable Population [Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

   Tumor response was assessed by an IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.

10. DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable Population [Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

    DOR was defined as the time from the first occurrence of CR/PR to PD as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.

11. Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT Population [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

    Tumor response was assessed by the investigator according to immune-modified RECIST. PD was defined as >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm.

12. PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT Population [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

    PFS was defined as the time from randomization to PD, as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

13. Percentage of Participants With an Objective Response of CR or PR as Determined by the Investigator According to Immune-Modified RECIST in ORR-Evaluable Population [Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

    Tumor response was assessed by the investigator according to immune-modified RECIST. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.

14. DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable Population [Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

    DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.

15. Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT Population [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

    Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.

16. PFS as Determined by the Investigator According to RECIST v1.1 in ITT Population [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

    PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

17. Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in Participants With Sarcomatoid Histology [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

    Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.

18. PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid Histology [Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)]

    PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

19. Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid Histology [Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)]

    Percentage of participants who died of any cause was reported.

20. OS in Participants With Sarcomatoid Histology [Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)]

    OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

21. Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II Score [Baseline (Day 1 Cycle 1); Day 22 Cycle 1; Day 1 and 22 of every cycle from Cycle 2 up to Cycle 19; Cycle length = 42 days]

    The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part II, participants were asked to rate how much the symptoms have interfered with 6 areas of function (general activity, walking, work, mood, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely) and total Part II score was calculated as an average of 6-item scores. Repeated measures model-estimated least-squares (LS) mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement. Here, 'Number Analyzed' = number of participants evaluable at specified time point.

22. Change From Baseline in Symptom Severity as Determined by MDASI Part I Score [Baseline; End of Treatment (EoT) visit (up to approximately 27 months)]

    The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part I, participants were asked to rate how severe the symptoms (pain, fatigue, nausea, disturbed sleep, feeling of being distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, feeling sad, vomiting, numbness or tingling, rash/skin changes, headache, mouth/throat sores, and diarrhea) were when "at their worst" in the last 24 hours. Each item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Mixed-effects model-estimated LS mean score for change from baseline at the end-of treatment is reported for each item, where a negative value indicates improvement.

23. Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale Score [Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days]

    The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI interference subscale (6 items) assessed the impact of fatigue on global domains (general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely). Change from baseline in the mean score of all 6 items at each timepoint is reported, where a negative value indicates improvement.

24. Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue Item [Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days]

    The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI worst fatigue item assessed the severity of fatigue at its worst in the last 24 hours. The item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Change from baseline in the score at each time point is reported, where a negative value indicates improvement.

25. Change From Baseline in Treatment Side Effects Burden as Determined by Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-19) General Population 5 (GP5) Item Score [Day 1 and 22 of every cycle (Baseline = Day 1 Cycle 1) up to Cycle 19; Cycle length = 42 days]

    The FKSI-19 is a 19-item tool designed to assess the most important symptoms and concerns related to treatment effectiveness in advanced kidney cancer. The FKSI-19 GP5 item (bothered by the side effect of treatment) assessed side effects burden in the past 7 days on a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Repeated measures model-estimated LS mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement.

26. Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab [Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycles 2, 4, and 8, and every eight cycles thereafter up to EoT [up to approximately 27 months] and 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days)]

    The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against atezolizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result. Here, 'Overall Number of Participants Analyzed' = number of participants with a non-missing baseline ATA sample; 'Number Analyzed' = number of participants with a non-missing ATA sample at indicated timepoint.

27. Number of Participants With ATAs Against Bevacizumab [Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycle 3, at EoT [up to approximately 27 months] and at 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days)]

    The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against bevacizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.

28. Maximum Observed Serum Concentration (Cmax) for Atezolizumab [30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days)]

    Cmax for atezolizumab was estimated from plasma concentration versus time data.

29. Minimum Observed Serum Concentration (Cmin) for Atezolizumab [Predose (Hour 0) on Day 22 of Cycle 1; predose (Hour 0) on Day 1 of Cycles 2; Cycle length = 42 days]

    Cmin for atezolizumab was estimated from plasma concentration versus time data.

30. Cmax for Bevacizumab [30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days)]

    Cmax for bevacizumab was estimated from plasma concentration versus time data.

31. Cmin for Bevacizumab [Pre-dose (Hour 0) on Day 1 of Cycle 3 (Cycle length = 42 days)]

    Cmin for bevacizumab was estimated from plasma concentration versus time data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Definitive diagnosis of unresectable locally advanced or metastatic RCC with clear-cell histology and/or a component of sarcomatoid carcinoma, with no prior treatment in the metastatic setting

• Evaluable Memorial Sloan Kettering Cancer Center risk score

• Measurable disease, as defined by RECIST v1.1

• Karnofsky performance status greater than or equal to 70%

• Adequate hematologic and end-organ function prior to randomization

Exclusion Criteria:

Disease-Specific Exclusions:

• Radiotherapy for RCC within 14 days prior to treatment

• Active central nervous system disease

• Uncontrolled pleural effusion, pericardial effusion, or ascites

• Uncontrolled hypercalcemia

• Any other malignancies within 5 years except for low-risk prostate cancer or those with negligible risk of metastasis or death

General Medical Exclusions:

• Life expectancy less than 12 weeks

• Participation in another experimental drug study within 4 weeks prior to treatment

• Pregnant or lactating women

• Known hypersensitivity to any component of atezolizumab or other study medication

• History of autoimmune disease except controlled, treated hypothyroidism or type I diabetes mellitus

• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis

• Positive human immunodeficiency virus test

• Active or chronic hepatitis B or C

• Severe infections within 4 weeks prior to treatment

• Exposure to oral or IV antibiotics within 2 weeks prior to treatment

• Live attenuated vaccines within 4 weeks prior to treatment (for influenza vaccination participants must agree not to receive live, attenuated influenza vaccine within 4 weeks prior to treatment, during treatment or within 5 months following the last dose)

• Significant cardiovascular disease

• Prior allogeneic stem cell or solid organ transplantation

Exclusion Criteria Related to Medications:

• Prior treatment with cluster of differentiation 137 agonists, anti-cytotoxic T-lymphocyte associated protein-4, anti-programmed death (PD)-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents

• Treatment with immunostimulatory agents for non-malignant conditions within 6 weeks or immunosuppressive agents within 2 weeks prior to treatment

Bevacizumab- and Sunitinib-Specific Exclusions:

• History of hypertensive crisis or hypertensive encephalopathy

• Baseline electrocardiogram showing corrected QT interval greater than 460 milliseconds

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center	Tucson	Arizona	United States	85719
2	University of California at Irvine Medical Center; Department of Oncology	Orange	California	United States	92868
3	University of California	San Francisco	California	United States	94158
4	University of Colorado; Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
5	Rocky Mountain Cancer Center; Medical Oncology	Boulder	Colorado	United States	80303
6	Georgetown U; Lombardi Comp Can	Washington	District of Columbia	United States	20016-1468
7	Lynn Cancer Institute/Boca Raton Regional Hospital	Boca Raton	Florida	United States	33486
8	Florida Cancer Specialists - Port Charlotte	Port Charlotte	Florida	United States	33980
9	Florida Cancer Specialist, North Region	Saint Petersburg	Florida	United States	33705
10	Piedmont Cancer Institute, PC	Atlanta	Georgia	United States	30318
11	The University of Chicago	Chicago	Illinois	United States	60637
12	Norton Cancer Institute	Louisville	Kentucky	United States	40202
13	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
14	Dana Farber Cancer Inst.	Boston	Massachusetts	United States	02115
15	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
16	Comprehensive Cancer Centers of Nevada - Eastern Avenue	Las Vegas	Nevada	United States	89169
17	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
18	New York Oncology Hematology,P.C.-Albany	Albany	New York	United States	12208
19	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
20	Oncology Hematology Care Inc	Cincinnati	Ohio	United States	45242
21	Cleveland Clinic Foundation; Taussig Cancer Center	Cleveland	Ohio	United States	44195
22	Northwest Cancer Specialists, P.C.	Tigard	Oregon	United States	97223
23	SCRI Tennessee Oncology Chattanooga	Chattanooga	Tennessee	United States	37404
24	Sarah Cannon Cancer Center and Research Institute	Nashville	Tennessee	United States	37203
25	Vanderbilt Univ Medical Ctr	Nashville	Tennessee	United States	37232
26	Texas Oncology-Baylor Sammons Cancer Center	Dallas	Texas	United States	75246
27	Oncology and Hematology Associates of SW Virginia-Raonoke	Roanoke	Virginia	United States	24014
28	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
29	Lifehouse	Camperdown	New South Wales	Australia	2050
30	Macquarie University Hospital	Macquarie Park	New South Wales	Australia	2109
31	Calvary Mater Newcastle; Medical Oncology	Waratah	New South Wales	Australia	2298
32	Icon Cancer Foundation	South Brisbane	Queensland	Australia	4101
33	Ashford Cancer Center Research	Kurralta Park	South Australia	Australia	5037
34	Austin Hospital; Medical Oncology	Heidelberg	Victoria	Australia	3084
35	St John of God Hospital	Murdoch	Western Australia	Australia	6150
36	University Clinical Centre of the Republic of Srpska	Banja Luka		Bosnia and Herzegovina	78000
37	Hospital de Caridade de Ijui; Oncologia	Ijui	RS	Brazil	98700-000
38	Santa Casa de Misericordia de Porto Alegre	Porto Alegre	RS	Brazil	90050-170
39	Hospital Sao Lucas - PUCRS	Porto Alegre	RS	Brazil	90610-000
40	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP	Brazil	01246-000
41	Queen Elizabeth II Health Sciences Centre; Oncology	Halifax	Nova Scotia	Canada	B3H 2Y9
42	Royal Victoria Hospital	Barrie	Ontario	Canada	L4M 6M2
43	Hamilton Health Sciences - Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
44	London Regional Cancer Centre	London	Ontario	Canada	N6A 4L6
45	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario	Canada	L1G 2B9
46	The Ottawa Hospital Cancer Centre; Oncology	Ottawa	Ontario	Canada	K1H 8L6
47	Sunnybrook Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
48	Princess Margaret Cancer Center	Toronto	Ontario	Canada	M5G 1Z5
49	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
50	CHU de Quebec Hotel-Dieu de Quebec	Quebec City	Quebec	Canada	G1R 2J6
51	Masarykuv onkologicky ustav	Brno		Czechia	656 53
52	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc		Czechia	779 00
53	Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika	Praha 2		Czechia	128 08
54	Thomayerova nemocnice	Praha 4 - Krc		Czechia	140 59
55	Aarhus Universitetshospital; Kræftafdelingen	Aarhus N		Denmark	8200
56	Herlev Hospital; Afdeling for Kræftbehandling	Herlev		Denmark	2730
57	Odense Universitetshospital, Onkologisk Afdeling R	Odense C		Denmark	5000
58	ICO Paul Papin; Oncologie Medicale.	Angers		France	49055
59	Hopital Saint Andre; Oncologie 2	Bordeaux		France	33075
60	Centre Francois Baclesse; Urologie Gynecologie	Caen		France	14076
61	Centre Oscar Lambret	Lille		France	59020
62	Centre Léon Bérard	Lyon		France	69373
63	Institut Paoli Calmettes; Oncologie Medicale	Marseille		France	13273
64	Centre D'Oncologie de Gentilly; Oncology	Nancy		France	54100
65	APHP - Hospital Saint Louis	Paris		France	75475
66	Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale	Paris		France	75908
67	ICO - Site René Gauducheau	Saint Herblain		France	44805
68	Institut Gustave Roussy; Departement Oncologie Medicale	Villejuif		France	94805
69	Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie	Dresden		Germany	01307
70	Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung	Essen		Germany	45122
71	Nationales Centrum für Tumorerkrankungen Heidelberg (NCT); Thoraxklinik Heidelberg	Heidelberg		Germany	69120
72	Klinikum d.Universität München Campus Großhadern	München		Germany	81377
73	Universitätsklinikum Tübingen; Klinik für Urologie	Tübingen		Germany	72076
74	Az. Osp. Cardarelli; Divisione Di Oncologia	Napoli	Campania	Italy	80131
75	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna	Italy	47014
76	A.O. Universitaria Policlinico Di Modena; Oncologia	Modena	Emilia-Romagna	Italy	41100
77	Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica	Roma	Lazio	Italy	00152
78	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia	Italy	20132
79	Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia	Milano	Lombardia	Italy	20162
80	Fondazione IRCCS Policlinico San Matteo, Oncologia	Pavia	Lombardia	Italy	27100
81	Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia	Arezzo	Toscana	Italy	52100
82	Nagoya University Hospital; Urology	Aichi		Japan	466-8560
83	Chiba Cancer Center	Chiba		Japan	260-8717
84	Kyushu University Hospital	Fukuoka		Japan	812-8582
85	Gunma University Hospital	Gunma		Japan	371-8511
86	Hokkaido University Hospital	Hokkaido		Japan	060-8648
87	University of Tsukuba Hospital; Urology	Ibaraki		Japan	305-8576
88	Iwate Medical University Hospital	Iwate		Japan	028-3695
89	Yokohama City University Hospital	Kanagawa		Japan	236-0004
90	Kitasato University Hospital	Kanagawa		Japan	252-0375
91	Kumamoto University Hospital	Kumamoto		Japan	860-8556
92	Niigata University Medical & Dental Hospital	Niigata		Japan	951-8520
93	Okayama University Hospital	Okayama		Japan	700-8558
94	Osaka International Cancer Institute; Urology	Osaka		Japan	541-8567
95	Osaka City University Hospital	Osaka		Japan	545-8586
96	Osaka University Hospital	Osaka		Japan	565-0871
97	Kindai University Hospital	Osaka		Japan	589-8511
98	Tokushima University Hospital	Tokushima		Japan	770-8503
99	Toranomon Hospital	Tokyo		Japan	105-8470
100	Tokyo Medical and Dental University Hospital	Tokyo		Japan	113-8519
101	Nippon Medical School Hospital	Tokyo		Japan	113-8603
102	The Cancer Institute Hospital, JFCR; Urology	Tokyo		Japan	135-8550
103	Keio University Hospital	Tokyo		Japan	160-8582
104	Tokyo Women's Medical University	Tokyo		Japan	162-0054
105	Chungnam National University Hospital	Daejeon		Korea, Republic of	35015
106	National Cancer Center	Goyang-si		Korea, Republic of	10408
107	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13605
108	Seoul National University Hospital	Seoul		Korea, Republic of	03080
109	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
110	Asan Medical Center	Seoul		Korea, Republic of	05505
111	Samsung Medical Center	Seoul		Korea, Republic of	06351
112	Cancerología	Queretaro		Mexico	76090
113	Centro Oncologico Estatal ISSEMYM	Toluca		Mexico	50180
114	Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli	Lublin		Poland	20-090
115	Szpital Kliniczny; Przemienienia Panskiego;Uniwersytetu Medyczny im.; Karola Marcinkowskiego w Pozna	Poznan		Poland	60-569
116	Saint Elizabeth's Hospital	Warsaw		Poland	02-616
117	MAGODENT Sp. z o.o.	Warsaw		Poland	04-125
118	ALTAI REGIONAL ONCOLOGICAL CENTER; "Nadezhda" Clinic	Barnaul	Altaj	Russian Federation	656049
119	GBUZ Nizhegorodskay Region: Clinical Diagnostic Center	Nizhni Novgorod	Niznij Novgorod	Russian Federation	603001
120	P.A. Herzen Oncological Inst. ; Oncology	Moscow		Russian Federation	125284
121	City Clinical Oncology Hospital	Moscow		Russian Federation	143423
122	National University Hospital	Singapore		Singapore	119074
123	National Cancer Centre; Medical Oncology	Singapore		Singapore	169610
124	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona	Spain	8208
125	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba	Spain	14004
126	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona		Spain	08035
127	Hospital Clínic i Provincial; Servicio de Oncología	Barcelona		Spain	08036
128	Hospital Duran i Reynals; Oncologia	Barcelona		Spain	08907
129	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid		Spain	28007
130	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid		Spain	28034
131	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid		Spain	28041
132	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla		Spain	41013
133	Taichung Veterans General Hospital; Division of Urology	Taichung		Taiwan	407
134	National Taiwan Uni Hospital; Dept of Oncology	Taipei		Taiwan	100
135	Chang Gung Medical Foundation-Linkou, Urinary Oncology	Taoyuan		Taiwan	333
136	Chulalongkorn Hospital; Medical Oncology	Bangkok		Thailand	10330
137	Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc	Bangkok		Thailand	10400
138	Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology	Bangkok		Thailand	10700
139	Maharaj Nakorn Chiangmai Hospital; Department of Surgery/ Urology unit	Chiangmai		Thailand	50200
140	Songklanagarind Hospital; Department of Oncology	Songkhla		Thailand	90110
141	Hacettepe University Medical Faculty	Ankara		Turkey	06100
142	Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department	Edirne		Turkey	22770
143	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul		Turkey	34300
144	Clatterbridge Cancer Centre	Bebington		United Kingdom	CH63 4JY
145	Queen Elizabeth Hospital	Birmingham		United Kingdom	B15 2TH
146	Royal Blackburn Hospital	Blackburn		United Kingdom	BB2 3HH
147	Addenbrookes Nhs Trust; Oncology Clinical Trials Unit	Cambridge		United Kingdom	CB2 0QQ
148	Barts Health NHS Trust - St Bartholomew's Hospital	London		United Kingdom	EC1A 7BE
149	Royal Free Hospital; Dept of Oncology	London		United Kingdom	NW3 2QG
150	Christie Hospital Nhs Trust; Medical Oncology	Manchester		United Kingdom	M2O 4BX
151	Churchill Hospital; Oxford Cancer and Haematology Centre	Oxford		United Kingdom	OX3 7LJ
152	Southampton General Hospital; Medical Oncology	Southampton		United Kingdom	SO16 6YD
153	Royal Marsden Hospital; Dept of Medical Oncology	Sutton		United Kingdom	SM2 5PT
154	Singleton Hospital; Pharmacy Department	Swansea		United Kingdom	SA2 8QA

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 3, 2018

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02420821
• Other Study ID Numbers: WO29637; 2014-004684-20
• First Posted: Apr 20, 2015
• Last Update Posted: Jan 24, 2022
• Last Verified: Jan 1, 2022

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Bevacizumab; Sunitinib; Atezolizumab; Antibodies; Antibodies, Monoclonal

Study Results

Participant Flow

Pre-assignment Detail	A total of 1228 participants were screened, out of which, 915 participants were enrolled into the study.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 milligrams (mg) administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to disease progression (PD) as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 milligrams per kilogram (mg/kg) administered via intravenous (IV) infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Period Title: Overall Study
STARTED	461	454
COMPLETED	293	317
NOT COMPLETED	168	137

Baseline Characteristics

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab	Total
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Total of all reporting groups
Overall Participants	461	454	915
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.9 (9.9)	61.6 (10.4)	60.7 (10.2)
Sex: Female, Male (Count of Participants)
Female	109 23.6%	137 30.2%	246 26.9%
Male	352 76.4%	317 69.8%	669 73.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	32 6.9%	25 5.5%	57 6.2%
Not Hispanic or Latino	386 83.7%	391 86.1%	777 84.9%
Unknown or Not Reported	43 9.3%	38 8.4%	81 8.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.2%	2 0.4%	3 0.3%
Asian	77 16.7%	94 20.7%	171 18.7%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.2%	1 0.1%
Black or African American	4 0.9%	1 0.2%	5 0.5%
White	334 72.5%	326 71.8%	660 72.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	45 9.8%	30 6.6%	75 8.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Disease Progression as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death From Any Cause in Programmed Death-Ligand 1 (PD-L1)-Selected Population
Description	Tumor response was assessed by the investigator according to RECIST v1.1. Disease Progression (PD) was defined as greater than or equal to (>/=) 20 percent (%) relative increase in the sum of diameters (SoD) of all target lesions (TLs), taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 millimeters (mm); >/=1 new lesion(s); and/or unequivocal progression of existing non-TLs.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PD-L1-Selected Population, which included all participants in the ITT population whose PD-L1 status was immune cell (IC)1/2/3 at the time of randomization.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	184	178
Number [percentage of participants]	69.6 15.1%	58.4 12.9%

2. Primary Outcome

Title	Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected Population
Description	PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% confidence interval (CI) was assessed using the method of Brookmeyer and Crowley.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PD-L1-Selected Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	184	178
Median (95% Confidence Interval) [months]	7.5	11.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0205
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.57 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression.

3. Primary Outcome

Title	Percentage of Participants Who Died of Any Cause in ITT Population
Description	Percentage of participants who died of any cause was reported.
Time Frame	Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	461	454
Number [percentage of participants]	30.6 6.6%	27.1 6%

4. Primary Outcome

Title	Overall Survival (OS) in ITT Population
Description	OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame	Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	461	454
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0895
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.63 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression.

5. Secondary Outcome

Title	Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population
Description	Percentage of participants who died of any cause was reported.
Time Frame	Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PD-L1-Selected Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	184	178
Number [percentage of participants]	34.8 7.5%	25.3 5.6%

6. Secondary Outcome

Title	OS in PD-L1-Selected Population
Description	OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame	Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PD-L1-Selected Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	184	178
Median (95% Confidence Interval) [months]	23.3	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0470
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.46 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression.

7. Secondary Outcome

Title	Percentage of Participants With PD as Determined by an Independent Review Committee (IRC) According to RECIST v1.1 or Death From Any Cause in ITT Population
Description	Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	461	454
Number [percentage of participants]	63.6 13.8%	60.4 13.3%

8. Secondary Outcome

Title	PFS as Determined by an IRC According to RECIST v1.1 in ITT Population
Description	PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	461	454
Median (95% Confidence Interval) [months]	8.3	9.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1218
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression.

9. Secondary Outcome

Title	Percentage of Participants With PD as Determined by an IRC According to RECIST v1.1 or Death From Any Cause in PD-L1-Selected Population
Description	Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PD-L1-Selected Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	184	178
Number [percentage of participants]	64.7 14%	62.9 13.9%

10. Secondary Outcome

Title	PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected Population
Description	PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PD-L1-Selected Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	184	178
Median (95% Confidence Interval) [months]	7.2	8.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6138
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression.

11. Secondary Outcome

Title	Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator According to RECIST v1.1 in Objective Response Rate (ORR)-Evaluable Population
Description	Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to less than (<) 10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
Time Frame	Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ORR-Evaluable Population, which included all participants in the ITT population with measurable disease at baseline, as determined by the investigator.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	460	454
Number (95% Confidence Interval) [percentage of participants]	33.3 7.2%	36.6 8.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2733
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	3.30
	Confidence Interval	(2-Sided) 95%; -3.09 to 9.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in response rates was constructed using Wald method.

12. Secondary Outcome

Title	Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable Population
Description	DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
Time Frame	Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on DOR-Evaluable Population, which included all participants with a CR/PR in the ORR-Evaluable Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	153	166
Median (95% Confidence Interval) [months]	14.2	16.6

13. Secondary Outcome

Title	Percentage of Participants With an Objective Response of CR or PR as Determined by an IRC According to RECIST v1.1 in ORR-Evaluable Population
Description	Tumor response was assessed by an IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
Time Frame	Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ORR-Evaluable Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	460	454
Number (95% Confidence Interval) [percentage of participants]	31.3 6.8%	33.3 7.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5121
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	1.96
	Confidence Interval	(2-Sided) 95%; -4.32 to 8.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in response rates was constructed using Wald method.

14. Secondary Outcome

Title	DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable Population
Description	DOR was defined as the time from the first occurrence of CR/PR to PD as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
Time Frame	Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the DOR-Evaluable Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	144	151
Median (95% Confidence Interval) [months]	18.6	NA

15. Secondary Outcome

Title	Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT Population
Description	Tumor response was assessed by the investigator according to immune-modified RECIST. PD was defined as >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	461	454
Number [percentage of participants]	58.1 12.6%	55.1 12.1%

16. Secondary Outcome

Title	PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT Population
Description	PFS was defined as the time from randomization to PD, as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	461	454
Median (95% Confidence Interval) [months]	12.3	13.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0606
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression.

17. Secondary Outcome

Title	Percentage of Participants With an Objective Response of CR or PR as Determined by the Investigator According to Immune-Modified RECIST in ORR-Evaluable Population
Description	Tumor response was assessed by the investigator according to immune-modified RECIST. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
Time Frame	Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ORR-Evaluable Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	460	454
Number (95% Confidence Interval) [percentage of participants]	35.0 7.6%	40.1 8.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1011
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	5.09
	Confidence Interval	(2-Sided) 95%; -1.40 to 11.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in response rates was constructed using Wald method.

18. Secondary Outcome

Title	DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable Population
Description	DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
Time Frame	Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on DOR-Evaluable Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	161	182
Median (95% Confidence Interval) [months]	19.4	19.4

19. Secondary Outcome

Title	Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT Population
Description	Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	461	454
Number [percentage of participants]	63.8 13.8%	60.1 13.2%

20. Secondary Outcome

Title	PFS as Determined by the Investigator According to RECIST v1.1 in ITT Population
Description	PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	461	454
Median (95% Confidence Interval) [months]	8.4	11.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0254
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.70 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression.

21. Secondary Outcome

Title	Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in Participants With Sarcomatoid Histology
Description	Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population participants with sarcomatoid histology (defined by investigator-assessed conventional histopathology).

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	74	68
Number [percentage of participants]	85.1 18.5%	67.6 14.9%

22. Secondary Outcome

Title	PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid Histology
Description	PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame	Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population participants with sarcomatoid histology.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	74	68
Median (95% Confidence Interval) [months]	5.3	8.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.34 to 0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression.

23. Secondary Outcome

Title	Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid Histology
Description	Percentage of participants who died of any cause was reported.
Time Frame	Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population participants with sarcomatoid histology.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	74	68
Number [percentage of participants]	50.0 10.8%	38.2 8.4%

24. Secondary Outcome

Title	OS in Participants With Sarcomatoid Histology
Description	OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame	Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT Population participants with sarcomatoid histology.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	74	68
Median (95% Confidence Interval) [months]	15.0	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0323
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; 0.32 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was estimated by Cox regression.

25. Secondary Outcome

Title	Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II Score
Description	The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part II, participants were asked to rate how much the symptoms have interfered with 6 areas of function (general activity, walking, work, mood, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely) and total Part II score was calculated as an average of 6-item scores. Repeated measures model-estimated least-squares (LS) mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement. Here, 'Number Analyzed' = number of participants evaluable at specified time point.
Time Frame	Baseline (Day 1 Cycle 1); Day 22 Cycle 1; Day 1 and 22 of every cycle from Cycle 2 up to Cycle 19; Cycle length = 42 days

Outcome Measure Data

Analysis Population Description

Analysis was performed on the patient-reported outcome (PRO)-Evaluable Population, which included all participants with a non-missing baseline PRO assessment and >/=1 post-baseline PRO assessment.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	359	373
Change at Cycle1 Day 22	1.28 (0.13)	0.54 (0.13)
Change at Cycle 2 Day 1	0.76 (0.13)	0.56 (0.13)
Change at Cycle 2 Day 22	1.58 (0.13)	0.56 (0.13)
Change at Cycle 3 Day 1	1.05 (0.13)	0.53 (0.13)
Change at Cycle 3 Day 22	1.63 (0.14)	0.61 (0.13)
Change at Cycle 4 Day 1	1.02 (0.14)	0.59 (0.13)
Change at Cycle 4 Day 22	1.55 (0.14)	0.57 (0.14)
Change at Cycle 5 Day 1	1.18 (0.15)	0.72 (0.14)
Change at Cycle 5 Day 22	1.56 (0.15)	0.78 (0.14)
Change at Cycle 6 Day 1	1.03 (0.15)	0.82 (0.14)
Change at Cycle 6 Day 22	1.44 (0.15)	0.80 (0.15)
Change at Cycle 7 Day 1	1.15 (0.16)	0.72 (0.15)
Change at Cycle 7 Day 22	1.43 (0.16)	0.66 (0.15)
Change at Cycle 8 Day 1	1.06 (0.16)	0.76 (0.15)
Change at Cycle 8 Day 22	1.34 (0.17)	0.69 (0.15)
Change at Cycle 9 Day 1	1.05 (0.17)	0.67 (0.16)
Change at Cycle 9 Day 22	1.46 (0.18)	0.56 (0.16)
Change at Cycle 10 Day 1	1.24 (0.18)	0.61 (0.16)
Change at Cycle 10 Day 22	1.61 (0.20)	0.60 (0.17)
Change at Cycle 11 Day 1	1.12 (0.19)	0.62 (0.17)
Change at Cycle 11 Day 22	1.45 (0.21)	0.61 (0.18)
Change at Cycle 12 Day 1	1.02 (0.21)	0.53 (0.18)
Change at Cycle 12 Day 22	1.45 (0.24)	0.69 (0.20)
Change at Cycle 13 Day 1	0.79 (0.24)	0.80 (0.21)
Change at Cycle 13 Day 22	1.09 (0.27)	0.73 (0.22)
Change at Cycle 14 Day 1	0.86 (0.27)	0.73 (0.24)
Change at Cycle 14 Day 22	1.22 (0.31)	0.83 (0.25)
Change at Cycle 15 Day 1	0.93 (0.31)	0.78 (0.27)
Change at Cycle 15 Day 22	1.67 (0.37)	0.88 (0.29)
Change at Cycle 16 Day 1	0.90 (0.38)	0.98 (0.32)
Change at Cycle 16 Day 22	1.30 (0.43)	1.32 (0.36)
Change at Cycle 17 Day 1	0.80 (0.46)	1.18 (0.40)
Change at Cycle 17 Day 22	0.92 (0.53)	0.95 (0.47)
Change at Cycle 18 Day 1	0.75 (0.64)	0.75 (0.53)
Change at Cycle 18 Day 22	0.65 (0.86)	0.87 (0.63)
Change at Cycle 19 Day 1	0.29 (1.58)	0.80 (0.73)
Change at Cycle 19 Day 22	0.88 (1.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 1 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.74
	Confidence Interval	(2-Sided) 95%; -1.06 to -0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 2 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2085
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.51 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 2 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95%; -1.33 to -0.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 3 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0013
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.51
	Confidence Interval	(2-Sided) 95%; -0.82 to -0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 3 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95%; -1.34 to -0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 4 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0098
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -0.76 to -0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 4 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95%; -1.32 to -0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 5 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0080
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -0.80 to -0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 5 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.78
	Confidence Interval	(2-Sided) 95%; -1.13 to -0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 6 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2512
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.56 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 6 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 95%; -1.01 to -0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 7 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0247
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -0.80 to -0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 7 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95%; -1.15 to -0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 8 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1411
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.68 to 0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 8 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0014
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 95%; -1.05 to -0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 9 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0728
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -0.78 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 9 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.90
	Confidence Interval	(2-Sided) 95%; -1.32 to -0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 10 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0041
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.62
	Confidence Interval	(2-Sided) 95%; -1.05 to -0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 10 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.00
	Confidence Interval	(2-Sided) 95%; -1.46 to -0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 11 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0353
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -0.96 to -0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 11 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.85
	Confidence Interval	(2-Sided) 95%; -1.35 to -0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 12 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0582
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -1.01 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 12 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0089
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95%; -1.32 to -0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 13 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9575
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.57 to 0.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 13 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2745
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -1.01 to 0.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 14 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7088
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.81 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 14 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3077
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -1.13 to 0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 15 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7112
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.93 to 0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 15 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0837
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.79
	Confidence Interval	(2-Sided) 95%; -1.69 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 16 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8655
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.88 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 16 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9725
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -1.07 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 17 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5285
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; -0.80 to 1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 17 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9663
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -1.34 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 18 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9914
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -1.61 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 18 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8345
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95%; -1.85 to 2.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 19 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7725
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; -2.90 to 3.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

26. Secondary Outcome

Title	Change From Baseline in Symptom Severity as Determined by MDASI Part I Score
Description	The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part I, participants were asked to rate how severe the symptoms (pain, fatigue, nausea, disturbed sleep, feeling of being distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, feeling sad, vomiting, numbness or tingling, rash/skin changes, headache, mouth/throat sores, and diarrhea) were when "at their worst" in the last 24 hours. Each item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Mixed-effects model-estimated LS mean score for change from baseline at the end-of treatment is reported for each item, where a negative value indicates improvement.
Time Frame	Baseline; End of Treatment (EoT) visit (up to approximately 27 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PRO-Evaluable Population. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	337	358
Pain: Change at EoT	1.41 (0.15)	0.92 (0.15)
Fatigue: Change at EoT	1.83 (0.15)	1.20 (0.15)
Nausea: Change at EoT	1.20 (0.11)	0.29 (0.11)
Disturbed sleep: Change at EoT	0.71 (0.14)	0.19 (0.14)
Feelings of being distressed: Change at EoT	0.82 (0.14)	0.25 (0.14)
Shortness of breath: Change at EoT	1.15 (0.13)	0.58 (0.13)
Remembering things: Change at EoT	0.93 (0.12)	0.60 (0.11)
Lack of appetite: Change at EoT	1.59 (0.14)	0.40 (0.14)
Drowsy: Change at EoT	1.32 (0.14)	0.79 (0.14)
Dry mouth: Change at EoT	1.67 (0.15)	0.67 (0.15)
Feeling sad: Change at EoT	0.88 (0.14)	0.28 (0.14)
Vomiting: Change at EoT	0.66 (0.09)	0.08 (0.09)
Numbness or tingling: Change at EoT	1.01 (0.12)	0.67 (0.12)
Rash/skin changes: Change at EoT	2.08 (0.13)	1.00 (0.13)
Headache: Change at EoT	0.70 (0.11)	0.66 (0.11)
Mouth/throat sores: Change at EoT	1.76 (0.13)	0.74 (0.13)
Diarrhea: Change at EoT	1.37 (0.10)	0.29 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Pain: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -0.77 to -0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Fatigue: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.63
	Confidence Interval	(2-Sided) 95%; -0.91 to -0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Nausea: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.91
	Confidence Interval	(2-Sided) 95%; -1.13 to -0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Disturbed sleep: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -0.79 to -0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Feelings of being distressed: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) 95%; -0.84 to -0.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Shortness of breath: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) 95%; -0.81 to -0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Remembering things: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0036
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -0.56 to -0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Lack of appetite: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.19
	Confidence Interval	(2-Sided) 95%; -1.46 to -0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Drowsy: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95%; -0.81 to -0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Dry mouth: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.00
	Confidence Interval	(2-Sided) 95%; -1.28 to -0.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Feeling sad: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -0.87 to -0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Vomiting: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.58
	Confidence Interval	(2-Sided) 95%; -0.75 to -0.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Numbness or tingling: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0051
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95%; -0.58 to -0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Rash/Skin Changes: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.08
	Confidence Interval	(2-Sided) 95%; -1.33 to -0.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Headache: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6541
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Mouth/Throat Sores: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95%; -1.28 to -0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Diarrhea: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.07
	Confidence Interval	(2-Sided) 95%; -1.27 to -0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

27. Secondary Outcome

Title	Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale Score
Description	The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI interference subscale (6 items) assessed the impact of fatigue on global domains (general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely). Change from baseline in the mean score of all 6 items at each timepoint is reported, where a negative value indicates improvement.
Time Frame	Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PRO-Evaluable Population. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	368	381
Baseline	2.11 (2.23)	2.08 (2.38)
Change at Cycle 1 Day 8	0.30 (1.88)	0.37 (1.76)
Change at Cycle 1 Day 15	1.26 (2.49)	1.06 (2.42)
Change at Cycle 1 Day 22	1.34 (2.44)	0.57 (2.04)
Change at Cycle 1 Day 29	1.48 (2.63)	0.66 (2.28)
Change at Cycle 1 Day 36	0.95 (2.29)	0.74 (2.20)
Change at Cycle 2 Day 1	0.38 (2.03)	0.43 (2.09)
Change at Cycle 2 Day 8	0.63 (2.17)	0.68 (2.33)
Change at Cycle 2 Day 15	1.10 (2.35)	0.55 (2.29)
Change at Cycle 2 Day 22	1.24 (2.65)	0.26 (2.14)
Change at Cycle 2 Day 29	1.45 (2.61)	0.51 (2.14)
Change at Cycle 2 Day 36	1.11 (2.46)	0.43 (2.17)
Change at Cycle 3 Day 1	0.76 (2.27)	0.21 (2.12)
Change at Cycle 3 Day 22	1.43 (2.41)	0.36 (2.20)
Change at Cycle 4 Day 1	0.76 (2.27)	0.38 (2.16)
Change at Cycle 4 Day 22	1.47 (2.60)	0.44 (2.33)
Change at Cycle 5 Day 1	1.01 (2.46)	0.52 (2.31)
Change at Cycle 5 Day 22	1.38 (2.22)	0.61 (2.27)
Change at Cycle 6 Day 1	0.88 (2.24)	0.59 (2.15)
Change at Cycle 6 Day 22	1.25 (2.42)	0.52 (2.22)
Change at Cycle 7 Day 1	0.82 (2.35)	0.61 (2.17)
Change at Cycle 7 Day 22	1.05 (2.31)	0.47 (2.16)
Change at Cycle 8 Day 1	0.87 (2.21)	0.63 (2.36)
Change at Cycle 8 Day 22	1.22 (2.21)	0.52 (2.05)
Change at Cycle 9 Day 1	0.93 (2.25)	0.57 (2.27)
Change at Cycle 9 Day 22	1.35 (2.37)	0.37 (2.15)
Change at Cycle 10 Day 1	1.09 (2.53)	0.56 (1.96)
Change at Cycle 10 Day 22	1.62 (2.75)	0.52 (1.95)
Change at Cycle 11 Day 1	0.95 (2.29)	0.60 (1.92)
Change at Cycle 11 Day 22	0.88 (2.57)	0.57 (1.78)
Change at Cycle 12 Day 1	0.89 (2.45)	0.35 (1.75)
Change at Cycle 12 Day 22	0.97 (2.46)	0.58 (1.96)
Change at Cycle 13 Day 1	0.84 (2.29)	0.36 (1.88)
Change at Cycle 13 Day 22	0.76 (2.70)	0.56 (2.06)
Change at Cycle 14 Day 1	0.80 (2.33)	0.73 (1.80)
Change at Cycle 14 Day 22	0.69 (2.73)	0.94 (1.96)
Change at Cycle 15 Day 1	0.95 (2.42)	0.61 (1.41)
Change at Cycle 15 Day 22	1.05 (3.22)	0.91 (1.28)
Change at Cycle 16 Day 1	0.13 (1.49)	1.02 (1.69)
Change at Cycle 16 Day 22	1.05 (1.83)	1.55 (1.96)
Change at Cycle 17 Day 1	0.53 (1.41)	1.25 (1.97)
Change at Cycle 17 Day 22	1.43 (2.16)	0.41 (1.48)
Change at Cycle 18 Day 1	0.79 (1.34)	0.35 (1.46)
Change at Cycle 18 Day 22	1.28 (2.21)	0.17 (1.15)
Change at Cycle 19 Day 1	0.00	-0.80 (0.84)
Change at Cycle 19 Day 22	-0.25 (0.82)
Change at 6 weeks after EoT	2.31 (2.52)	1.83 (2.52)
Change at 12 weeks after EoT	1.71 (2.66)	1.97 (2.63)
Change at 24 weeks after EoT	2.38 (3.11)	2.15 (3.30)
Change at 36 weeks after EoT	2.40 (3.32)	1.15 (2.72)
Change at EoT	1.57 (2.80)	1.62 (2.98)
Change Within 30 Days of PD	1.74 (2.64)	0.74 (2.35)

28. Secondary Outcome

Title	Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue Item
Description	The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI worst fatigue item assessed the severity of fatigue at its worst in the last 24 hours. The item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Change from baseline in the score at each time point is reported, where a negative value indicates improvement.
Time Frame	Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PRO-Evaluable Population. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	368	381
Baseline	3.08 (2.66)	2.98 (2.69)
Change at Cycle 1 Day 8	0.34 (2.35)	0.50 (2.29)
Change at Cycle 1 Day 15	1.32 (2.82)	1.26 (2.92)
Change at Cycle 1 Day 22	1.52 (2.86)	0.49 (2.30)
Change at Cycle 1 Day 29	1.55 (2.99)	0.88 (2.62)
Change at Cycle 1 Day 36	0.77 (2.82)	0.86 (2.50)
Change at Cycle 2 Day 1	0.40 (2.50)	0.45 (2.52)
Change at Cycle 2 Day 8	0.56 (2.68)	0.87 (2.82)
Change at Cycle 2 Day 15	1.09 (2.82)	0.71 (2.78)
Change at Cycle 2 Day 22	1.42 (3.01)	0.31 (2.53)
Change at Cycle 2 Day 29	1.43 (3.08)	0.62 (2.66)
Change at Cycle 2 Day 36	1.09 (3.01)	0.48 (2.76)
Change at Cycle 3 Day 1	0.42 (2.68)	0.40 (2.57)
Change at Cycle 3 Day 22	1.57 (2.98)	0.57 (2.64)
Change at Cycle 4 Day 1	0.64 (2.76)	0.54 (2.49)
Change at Cycle 4 Day 22	1.46 (3.14)	0.58 (2.74)
Change at Cycle 5 Day 1	0.81 (2.75)	0.62 (2.79)
Change at Cycle 5 Day 22	1.60 (2.87)	0.69 (2.83)
Change at Cycle 6 Day 1	0.90 (2.78)	0.86 (2.73)
Change at Cycle 6 Day 22	1.35 (2.79)	0.53 (2.66)
Change at Cycle 7 Day 1	0.79 (2.78)	0.79 (2.70)
Change at Cycle 7 Day 22	1.22 (2.85)	0.65 (2.56)
Change at Cycle 8 Day 1	0.79 (2.69)	0.75 (2.84)
Change at Cycle 8 Day 22	1.40 (2.64)	0.78 (2.67)
Change at Cycle 9 Day 1	0.97 (2.54)	0.61 (2.62)
Change at Cycle 9 Day 22	1.54 (2.92)	0.57 (2.55)
Change at Cycle 10 Day 1	0.95 (2.73)	0.69 (2.46)
Change at Cycle 10 Day 22	1.74 (3.09)	0.63 (2.48)
Change at Cycle 11 Day 1	0.73 (2.80)	0.74 (2.69)
Change at Cycle 11 Day 22	1.15 (3.18)	0.74 (2.52)
Change at Cycle 12 Day 1	0.78 (2.79)	0.61 (2.29)
Change at Cycle 12 Day 22	1.32 (2.89)	0.74 (2.69)
Change at Cycle 13 Day 1	0.35 (2.54)	0.49 (2.46)
Change at Cycle 13 Day 22	0.72 (3.48)	0.65 (2.70)
Change at Cycle 14 Day 1	0.56 (2.84)	0.81 (2.60)
Change at Cycle 14 Day 22	0.37 (3.01)	1.04 (2.40)
Change at Cycle 15 Day 1	0.52 (3.15)	0.93 (2.25)
Change at Cycle 15 Day 22	0.59 (4.08)	0.97 (1.84)
Change at Cycle 16 Day 1	-0.05 (2.61)	1.33 (1.92)
Change at Cycle 16 Day 22	0.77 (3.70)	1.68 (2.10)
Change at Cycle 17 Day 1	-0.62 (3.75)	1.68 (1.97)
Change at Cycle 17 Day 22	1.44 (3.91)	1.18 (1.99)
Change at Cycle 18 Day 1	0.00 (2.00)	1.33 (1.58)
Change at Cycle 18 Day 22	1.00 (1.73)	1.00 (2.10)
Change at Cycle 19 Day 1	-4.00	0.60 (1.34)
Change at Cycle 19 Day 22	0.00 (0.00)
Change at 6 weeks after EoT	2.43 (3.25)	2.40 (2.89)
Change at 12 weeks after EoT	1.56 (3.41)	2.06 (3.14)
Change at 24 weeks after EoT	1.58 (3.82)	1.92 (3.46)
Change at 36 weeks after EoT	1.86 (4.37)	0.78 (2.86)
Change at EoT	1.40 (3.13)	1.72 (2.84)
Change Within 30 Days of PD	1.81 (3.16)	0.89 (2.58)

29. Secondary Outcome

Title	Change From Baseline in Treatment Side Effects Burden as Determined by Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-19) General Population 5 (GP5) Item Score
Description	The FKSI-19 is a 19-item tool designed to assess the most important symptoms and concerns related to treatment effectiveness in advanced kidney cancer. The FKSI-19 GP5 item (bothered by the side effect of treatment) assessed side effects burden in the past 7 days on a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Repeated measures model-estimated LS mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement.
Time Frame	Day 1 and 22 of every cycle (Baseline = Day 1 Cycle 1) up to Cycle 19; Cycle length = 42 days

Outcome Measure Data

Analysis Population Description

Analysis was performed on the PRO-Evaluable Population. Here, 'Number Analyzed' = number of participants evaluable at specified time point.

Arm/Group Title	Sunitinib	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	359	373
Change at Cycle1 Day 22	-1.08 (0.06)	-0.36 (0.06)
Change at Cycle 2 Day 1	-0.87 (0.06)	-0.45 (0.06)
Change at Cycle 2 Day 22	-1.13 (0.06)	-0.43 (0.06)
Change at Cycle 3 Day 1	-1.07 (0.06)	-0.49 (0.06)
Change at Cycle 3 Day 22	-1.22 (0.06)	-0.45 (0.06)
Change at Cycle 4 Day 1	-1.07 (0.06)	-0.45 (0.06)
Change at Cycle 4 Day 22	-1.31 (0.07)	-0.49 (0.06)
Change at Cycle 5 Day 1	-1.17 (0.07)	-0.52 (0.06)
Change at Cycle 5 Day 22	-1.38 (0.07)	-0.55 (0.06)
Change at Cycle 6 Day 1	-1.14 (0.07)	-0.51 (0.06)
Change at Cycle 6 Day 22	-1.27 (0.07)	-0.56 (0.07)
Change at Cycle 7 Day 1	-1.09 (0.07)	-0.61 (0.07)
Change at Cycle 7 Day 22	-1.25 (0.07)	-0.58 (0.07)
Change at Cycle 8 Day 1	-1.08 (0.08)	-0.61 (0.07)
Change at Cycle 8 Day 22	-1.22 (0.08)	-0.62 (0.07)
Change at Cycle 9 Day 1	-1.08 (0.08)	-0.60 (0.07)
Change at Cycle 9 Day 22	-1.23 (0.08)	-0.52 (0.07)
Change at Cycle 10 Day 1	-1.06 (0.08)	-0.53 (0.07)
Change at Cycle 10 Day 22	-1.30 (0.09)	-0.57 (0.08)
Change at Cycle 11 Day 1	-1.16 (0.09)	-0.52 (0.08)
Change at Cycle 11 Day 22	-1.28 (0.11)	-0.54 (0.08)
Change at Cycle 12 Day 1	-1.05 (0.10)	-0.62 (0.09)
Change at Cycle 12 Day 22	-1.17 (0.12)	-0.56 (0.09)
Change at Cycle 13 Day 1	-1.15 (0.12)	-0.62 (0.10)
Change at Cycle 13 Day 22	-1.20 (0.14)	-0.64 (0.11)
Change at Cycle 14 Day 1	-0.94 (0.14)	-0.61 (0.12)
Change at Cycle 14 Day 22	-1.32 (0.16)	-0.65 (0.12)
Change at Cycle 15 Day 1	-0.91 (0.15)	-0.62 (0.13)
Change at Cycle 15 Day 22	-1.16 (0.19)	-0.72 (0.14)
Change at Cycle 16 Day 1	-1.06 (0.19)	-0.58 (0.16)
Change at Cycle 16 Day 22	-1.34 (0.22)	-0.41 (0.18)
Change at Cycle 17 Day 1	-1.10 (0.23)	-0.56 (0.20)
Change at Cycle 17 Day 22	-1.02 (0.27)	-0.44 (0.24)
Change at Cycle 18 Day 1	-1.01 (0.33)	-0.38 (0.27)
Change at Cycle 18 Day 22	-0.81 (0.46)	-0.48 (0.33)
Change at Cycle 19 Day 1	-1.27 (0.84)	-0.75 (0.38)
Change at Cycle 19 Day 22	-0.93 (0.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 1 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.58 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 2 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.42
	Confidence Interval	(2-Sided) 95%; 0.28 to 0.57
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 2 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.55 to 0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 3 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.44 to 0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 3 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.62 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 4 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.46 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 4 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.66 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 5 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.49 to 0.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 5 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.66 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 6 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; 0.46 to 0.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 6 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.54 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 7 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.47
	Confidence Interval	(2-Sided) 95%; 0.30 to 0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 7 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.49 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 8 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.47
	Confidence Interval	(2-Sided) 95%; 0.29 to 0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 8 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.41 to 0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 9 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; 0.29 to 0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 9 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.52 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 10 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; 0.33 to 0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 10 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.51 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 11 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; 0.41 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 11 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.49 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 12 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.42
	Confidence Interval	(2-Sided) 95%; 0.17 to 0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 12 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.32 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 13 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.23 to 0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 13 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; 0.23 to 0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 14 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0591
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.33
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 14 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.29 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 15 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1378
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 15 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0650
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 16 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0531
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.48
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 16 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.37 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 17 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0708
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; -0.05 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 17 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1078
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; -0.13 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 18 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1487
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; -0.22 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 18 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5537
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.33
	Confidence Interval	(2-Sided) 95%; -0.77 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Atezolizumab + Bevacizumab
	Comments	Cycle 19 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5743
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; -1.29 to 2.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.

30. Secondary Outcome

Title	Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab
Description	The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against atezolizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result. Here, 'Overall Number of Participants Analyzed' = number of participants with a non-missing baseline ATA sample; 'Number Analyzed' = number of participants with a non-missing ATA sample at indicated timepoint.
Time Frame	Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycles 2, 4, and 8, and every eight cycles thereafter up to EoT [up to approximately 27 months] and 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ATA-Evaluable Population, which included all participants in the Atezolizumab + Bevacizumab arm with a non-missing baseline ATA sample and >/=1 post-baseline ATA sample.

Arm/Group Title	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	446
Baseline: ATA Positive Participants	16 3.5%
Post-Baseline: Treatment-Induced ATA	95 20.6%
Post-Baseline: Treatment-Enhanced ATA	1 0.2%

31. Secondary Outcome

Title	Number of Participants With ATAs Against Bevacizumab
Description	The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against bevacizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.
Time Frame	Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycle 3, at EoT [up to approximately 27 months] and at 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ATA-Evaluable Population. Here, 'Overall Number of Participants Analyzed' = number of participants with a non-missing baseline ATA sample; 'Number Analyzed' = number of participants with a non-missing ATA sample at indicated timepoint.

Arm/Group Title	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	444
Baseline: ATA Positive Participants	24 5.2%
Post-Baseline: Treatment-Induced ATA	4 0.9%
Post-Baseline: Treatment-Enhanced ATA	0 0%

32. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) for Atezolizumab
Description	Cmax for atezolizumab was estimated from plasma concentration versus time data.
Time Frame	30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Atezolizumab Pharmacokinetic (PK) Population, which included all participants who received atezolizumab treatment and had evaluable PK samples. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	435
Mean (Standard Deviation) [micrograms per milliliter (mcg/mL)]	376 (90.2)

33. Secondary Outcome

Title	Minimum Observed Serum Concentration (Cmin) for Atezolizumab
Description	Cmin for atezolizumab was estimated from plasma concentration versus time data.
Time Frame	Predose (Hour 0) on Day 22 of Cycle 1; predose (Hour 0) on Day 1 of Cycles 2; Cycle length = 42 days

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Atezolizumab PK Population. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.

Arm/Group Title	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	426
Cycle 1 Day 22	85.6 (35.3)
Cycle 2 Day 1	127 (49.6)

34. Secondary Outcome

Title	Cmax for Bevacizumab
Description	Cmax for bevacizumab was estimated from plasma concentration versus time data.
Time Frame	30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Bevacizumab PK Population, which included all participants who received bevacizumab treatment and had evaluable PK samples. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	427
Mean (Standard Deviation) [mcg/mL]	339 (104)

35. Secondary Outcome

Title	Cmin for Bevacizumab
Description	Cmin for bevacizumab was estimated from plasma concentration versus time data.
Time Frame	Pre-dose (Hour 0) on Day 1 of Cycle 3 (Cycle length = 42 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Bevacizumab PK Population. Here, 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab + Bevacizumab
Arm/Group Description	Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Measure Participants	363
Mean (Standard Deviation) [mcg/mL]	135 (56.1)

Adverse Events

Time Frame	Baseline up to data cut-off date 29 September 2017(overall approximately 27 months)
Adverse Event Reporting Description	Analysis was performed on the safety-evaluable (SE) population, which included all randomized participants who received any amount of any component of the study treatments.
Arm/Group Title	Sunitinib		Atezolizumab + Bevacizumab
Arm/Group Description	Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.		Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
All Cause Mortality
	Sunitinib		Atezolizumab + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	135/446 (30.3%)		122/451 (27.1%)
Serious Adverse Events
	Sunitinib		Atezolizumab + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	149/446 (33.4%)		174/451 (38.6%)
Blood and lymphatic system disorders
Anaemia	3/446 (0.7%)		3/451 (0.7%)
Febrile neutropenia	2/446 (0.4%)		0/451 (0%)
Thrombocytopenia	4/446 (0.9%)		0/451 (0%)
Factor VIII inhibition	0/446 (0%)		1/451 (0.2%)
Cardiac disorders
Cardiac failure	0/446 (0%)		3/451 (0.7%)
Myocardial infarction	0/446 (0%)		3/451 (0.7%)
Acute coronary syndrome	1/446 (0.2%)		1/451 (0.2%)
Angina pectoris	1/446 (0.2%)		1/451 (0.2%)
Atrial fibrillation	0/446 (0%)		1/451 (0.2%)
Cardiac arrest	1/446 (0.2%)		1/451 (0.2%)
Myocarditis	0/446 (0%)		1/451 (0.2%)
Atrioventricular block complete	1/446 (0.2%)		0/451 (0%)
Ear and labyrinth disorders
Vertigo	0/446 (0%)		1/451 (0.2%)
Endocrine disorders
Adrenal insufficiency	0/446 (0%)		2/451 (0.4%)
Hypothyroidism	6/446 (1.3%)		1/451 (0.2%)
Gastrointestinal disorders
Diarrhoea	2/446 (0.4%)		7/451 (1.6%)
Abdominal pain	2/446 (0.4%)		4/451 (0.9%)
Colitis	1/446 (0.2%)		4/451 (0.9%)
Vomiting	5/446 (1.1%)		3/451 (0.7%)
Ileus	1/446 (0.2%)		2/451 (0.4%)
Abdominal pain upper	0/446 (0%)		1/451 (0.2%)
Autoimmune colitis	0/446 (0%)		1/451 (0.2%)
Constipation	1/446 (0.2%)		1/451 (0.2%)
Duodenal obstruction	0/446 (0%)		1/451 (0.2%)
Duodenal ulcer	1/446 (0.2%)		1/451 (0.2%)
Enteritis	0/446 (0%)		1/451 (0.2%)
Gastric haemorrhage	0/446 (0%)		1/451 (0.2%)
Gastrointestinal haemorrhage	1/446 (0.2%)		1/451 (0.2%)
Intestinal perforation	1/446 (0.2%)		1/451 (0.2%)
Large intestine perforation	0/446 (0%)		1/451 (0.2%)
Lower gastrointestinal haemorrhage	1/446 (0.2%)		1/451 (0.2%)
Nausea	3/446 (0.7%)		1/451 (0.2%)
Oesophageal perforation	0/446 (0%)		1/451 (0.2%)
Pancreatitis	2/446 (0.4%)		1/451 (0.2%)
Small intestinal haemorrhage	0/446 (0%)		1/451 (0.2%)
Small intestinal perforation	1/446 (0.2%)		1/451 (0.2%)
Stomatitis	1/446 (0.2%)		1/451 (0.2%)
Upper gastrointestinal haemorrhage	1/446 (0.2%)		1/451 (0.2%)
Anal fistula	1/446 (0.2%)		0/451 (0%)
Ascites	2/446 (0.4%)		0/451 (0%)
Gastrointestinal fistula	1/446 (0.2%)		0/451 (0%)
General disorders
Pyrexia	7/446 (1.6%)		12/451 (2.7%)
Asthenia	3/446 (0.7%)		3/451 (0.7%)
Influenza like illness	1/446 (0.2%)		3/451 (0.7%)
Systemic inflammatory response syndrome	0/446 (0%)		3/451 (0.7%)
Mucosal inflammation	0/446 (0%)		2/451 (0.4%)
Chest pain	4/446 (0.9%)		1/451 (0.2%)
Chills	0/446 (0%)		1/451 (0.2%)
Fatigue	2/446 (0.4%)		1/451 (0.2%)
General physical health deterioration	0/446 (0%)		1/451 (0.2%)
Ill-defined disorder	0/446 (0%)		1/451 (0.2%)
Infusion site extravasation	0/446 (0%)		1/451 (0.2%)
Malaise	1/446 (0.2%)		1/451 (0.2%)
Multiple organ dysfunction syndrome	0/446 (0%)		1/451 (0.2%)
Non-cardiac chest pain	0/446 (0%)		1/451 (0.2%)
Oedema	0/446 (0%)		1/451 (0.2%)
Pain	0/446 (0%)		1/451 (0.2%)
Performance status decreased	0/446 (0%)		1/451 (0.2%)
Death	1/446 (0.2%)		0/451 (0%)
Oedema peripheral	1/446 (0.2%)		0/451 (0%)
Hepatobiliary disorders
Autoimmune hepatitis	0/446 (0%)		4/451 (0.9%)
Biliary colic	0/446 (0%)		1/451 (0.2%)
Cholecystitis	1/446 (0.2%)		1/451 (0.2%)
Drug-induced liver injury	1/446 (0.2%)		1/451 (0.2%)
Hepatic function abnormal	1/446 (0.2%)		1/451 (0.2%)
Hepatic steatosis	0/446 (0%)		1/451 (0.2%)
Cholelithiasis	1/446 (0.2%)		0/451 (0%)
Hepatitis	1/446 (0.2%)		0/451 (0%)
Jaundice	1/446 (0.2%)		0/451 (0%)
Hepatotoxicity	1/446 (0.2%)		0/451 (0%)
Immune system disorders
Systemic immune activation	0/446 (0%)		3/451 (0.7%)
Cytokine release syndrome	0/446 (0%)		1/451 (0.2%)
Drug hypersensitivity	1/446 (0.2%)		1/451 (0.2%)
Hypersensitivity	0/446 (0%)		1/451 (0.2%)
Infections and infestations
Pneumonia	4/446 (0.9%)		7/451 (1.6%)
Sepsis	2/446 (0.4%)		3/451 (0.7%)
Diverticulitis	1/446 (0.2%)		2/451 (0.4%)
Infection	0/446 (0%)		2/451 (0.4%)
Lung infection	1/446 (0.2%)		2/451 (0.4%)
Upper respiratory tract infection	0/446 (0%)		2/451 (0.4%)
Urinary tract infection	1/446 (0.2%)		2/451 (0.4%)
Urosepsis	0/446 (0%)		2/451 (0.4%)
Cellulitis	1/446 (0.2%)		1/451 (0.2%)
Cystitis	0/446 (0%)		1/451 (0.2%)
Encephalitis	0/446 (0%)		1/451 (0.2%)
Haematoma infection	0/446 (0%)		1/451 (0.2%)
Herpes zoster	0/446 (0%)		1/451 (0.2%)
Lower respiratory tract infection	1/446 (0.2%)		1/451 (0.2%)
Lung abscess	0/446 (0%)		1/451 (0.2%)
Meningitis	0/446 (0%)		1/451 (0.2%)
Meningitis aseptic	0/446 (0%)		1/451 (0.2%)
Perirectal abscess	0/446 (0%)		1/451 (0.2%)
Peritonitis	0/446 (0%)		1/451 (0.2%)
Pilonidal cyst	0/446 (0%)		1/451 (0.2%)
Pyelonephritis	0/446 (0%)		1/451 (0.2%)
Respiratory tract infection	1/446 (0.2%)		1/451 (0.2%)
Septic shock	1/446 (0.2%)		1/451 (0.2%)
Subcutaneous abscess	0/446 (0%)		1/451 (0.2%)
Wound infection	0/446 (0%)		1/451 (0.2%)
Abscess	1/446 (0.2%)		0/451 (0%)
Appendicitis	2/446 (0.4%)		0/451 (0%)
Appendicitis perforated	1/446 (0.2%)		0/451 (0%)
Clostridium difficile infection	1/446 (0.2%)		0/451 (0%)
Device related infection	1/446 (0.2%)		0/451 (0%)
Empyema	1/446 (0.2%)		0/451 (0%)
Febrile infection	1/446 (0.2%)		0/451 (0%)
Gastroenteritis	1/446 (0.2%)		0/451 (0%)
Influenza	1/446 (0.2%)		0/451 (0%)
Orchitis	1/446 (0.2%)		0/451 (0%)
Osteomyelitis	1/446 (0.2%)		0/451 (0%)
Pneumonia viral	1/446 (0.2%)		0/451 (0%)
Scrotal abscess	1/446 (0.2%)		0/451 (0%)
Staphylococcal bacteraemia	1/446 (0.2%)		0/451 (0%)
Injury, poisoning and procedural complications
Conjunctival laceration	0/446 (0%)		1/451 (0.2%)
Fall	1/446 (0.2%)		1/451 (0.2%)
Femur fracture	2/446 (0.4%)		1/451 (0.2%)
Gastrointestinal anastomotic leak	0/446 (0%)		1/451 (0.2%)
Infusion related reaction	0/446 (0%)		1/451 (0.2%)
Post procedural haemorrhage	0/446 (0%)		1/451 (0.2%)
Upper limb fracture	0/446 (0%)		1/451 (0.2%)
Wound complication	0/446 (0%)		1/451 (0.2%)
Femoral neck fracture	1/446 (0.2%)		0/451 (0%)
Road traffic accident	1/446 (0.2%)		0/451 (0%)
Seroma	1/446 (0.2%)		0/451 (0%)
Tooth injury	1/446 (0.2%)		0/451 (0%)
Injury	0/446 (0%)		1/451 (0.2%)
Investigations
Blood creatinine increased	1/446 (0.2%)		2/451 (0.4%)
Blood creatine phosphokinase increased	0/446 (0%)		1/451 (0.2%)
Blood sodium decreased	0/446 (0%)		1/451 (0.2%)
Lipase increased	1/446 (0.2%)		1/451 (0.2%)
Liver function test increased	0/446 (0%)		1/451 (0.2%)
Weight decreased	0/446 (0%)		1/451 (0.2%)
Hepatic enzyme increased	1/446 (0.2%)		0/451 (0%)
Platelet count decreased	1/446 (0.2%)		0/451 (0%)
Troponin increased	1/446 (0.2%)		0/451 (0%)
Metabolism and nutrition disorders
Hyponatraemia	3/446 (0.7%)		4/451 (0.9%)
Dehydration	7/446 (1.6%)		3/451 (0.7%)
Hypercalcaemia	5/446 (1.1%)		3/451 (0.7%)
Hyperglycaemia	0/446 (0%)		2/451 (0.4%)
Hypoglycaemia	0/446 (0%)		2/451 (0.4%)
Cachexia	0/446 (0%)		1/451 (0.2%)
Decreased appetite	2/446 (0.4%)		1/451 (0.2%)
Diabetes mellitus inadequate control	0/446 (0%)		1/451 (0.2%)
Hyperkalaemia	0/446 (0%)		1/451 (0.2%)
Hypophosphataemia	1/446 (0.2%)		1/451 (0.2%)
Diabetes mellitus	1/446 (0.2%)		0/451 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/446 (0.2%)		4/451 (0.9%)
Arthralgia	1/446 (0.2%)		3/451 (0.7%)
Bone pain	1/446 (0.2%)		2/451 (0.4%)
Muscular weakness	0/446 (0%)		2/451 (0.4%)
Back pain	3/446 (0.7%)		1/451 (0.2%)
Joint swelling	0/446 (0%)		1/451 (0.2%)
Mobility decreased	0/446 (0%)		1/451 (0.2%)
Myalgia	0/446 (0%)		1/451 (0.2%)
Myositis	0/446 (0%)		1/451 (0.2%)
Bursitis	1/446 (0.2%)		0/451 (0%)
Fistula	1/446 (0.2%)		0/451 (0%)
Flank pain	1/446 (0.2%)		0/451 (0%)
Groin pain	1/446 (0.2%)		0/451 (0%)
Intervertebral disc protrusion	2/446 (0.4%)		0/451 (0%)
Muscle haemorrhage	1/446 (0.2%)		0/451 (0%)
Rhabdomyolysis	1/446 (0.2%)		0/451 (0%)
Musculoskeletal chest pain	1/446 (0.2%)		0/451 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon neoplasm	0/446 (0%)		1/451 (0.2%)
Prostate cancer	0/446 (0%)		1/451 (0.2%)
Tumour haemorrhage	0/446 (0%)		1/451 (0.2%)
Cholangiocarcinoma	1/446 (0.2%)		0/451 (0%)
Gastric cancer stage III	1/446 (0.2%)		0/451 (0%)
Intracranial tumour haemorrhage	1/446 (0.2%)		0/451 (0%)
Nervous system disorders
Haemorrhage intracranial	0/446 (0%)		2/451 (0.4%)
Ischaemic stroke	0/446 (0%)		2/451 (0.4%)
Syncope	2/446 (0.4%)		2/451 (0.4%)
Transient ischaemic attack	1/446 (0.2%)		2/451 (0.4%)
Altered state of consciousness	0/446 (0%)		1/451 (0.2%)
Aphasia	0/446 (0%)		1/451 (0.2%)
Cerebral infarction	0/446 (0%)		1/451 (0.2%)
Coma	0/446 (0%)		1/451 (0.2%)
Depressed level of consciousness	0/446 (0%)		1/451 (0.2%)
Dizziness	0/446 (0%)		1/451 (0.2%)
Gliosis	0/446 (0%)		1/451 (0.2%)
Haemorrhagic stroke	1/446 (0.2%)		1/451 (0.2%)
Intracranial pressure increased	0/446 (0%)		1/451 (0.2%)
Lethargy	0/446 (0%)		1/451 (0.2%)
Lumbosacral plexopathy	0/446 (0%)		1/451 (0.2%)
Neuropathy peripheral	0/446 (0%)		1/451 (0.2%)
Peripheral sensory neuropathy	0/446 (0%)		1/451 (0.2%)
Seizure	1/446 (0.2%)		1/451 (0.2%)
Spinal cord compression	0/446 (0%)		1/451 (0.2%)
Cerebral ischaemia	2/446 (0.4%)		0/451 (0%)
Cerebrovascular accident	1/446 (0.2%)		0/451 (0%)
Headache	2/446 (0.4%)		0/451 (0%)
Lacunar infarction	1/446 (0.2%)		0/451 (0%)
Paraplegia	1/446 (0.2%)		0/451 (0%)
Thalamus haemorrhage	1/446 (0.2%)		0/451 (0%)
Psychiatric disorders
Mental status changes	0/446 (0%)		2/451 (0.4%)
Psychotic disorder	0/446 (0%)		1/451 (0.2%)
Renal and urinary disorders
Acute kidney injury	10/446 (2.2%)		9/451 (2%)
Proteinuria	0/446 (0%)		3/451 (0.7%)
Renal failure	0/446 (0%)		2/451 (0.4%)
Haematuria	3/446 (0.7%)		1/451 (0.2%)
Nephritis	0/446 (0%)		1/451 (0.2%)
Renal impairment	0/446 (0%)		1/451 (0.2%)
Tubulointerstitial nephritis	0/446 (0%)		1/451 (0.2%)
Chronic kidney disease	1/446 (0.2%)		0/451 (0%)
Nephrolithiasis	1/446 (0.2%)		0/451 (0%)
Nephrotic syndrome	1/446 (0.2%)		0/451 (0%)
Ureteric obstruction	1/446 (0.2%)		0/451 (0%)
Urinary retention	1/446 (0.2%)		0/451 (0%)
Reproductive system and breast disorders
Prostatitis	1/446 (0.2%)		0/451 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	0/446 (0%)		7/451 (1.6%)
Dyspnoea	5/446 (1.1%)		4/451 (0.9%)
Pulmonary embolism	5/446 (1.1%)		4/451 (0.9%)
Pleural effusion	1/446 (0.2%)		3/451 (0.7%)
Acute respiratory failure	0/446 (0%)		2/451 (0.4%)
Hypoxia	1/446 (0.2%)		1/451 (0.2%)
Interstitial lung disease	0/446 (0%)		1/451 (0.2%)
Pleurisy	0/446 (0%)		1/451 (0.2%)
Pneumonia aspiration	0/446 (0%)		1/451 (0.2%)
Pulmonary infarction	0/446 (0%)		1/451 (0.2%)
Pulmonary pain	0/446 (0%)		1/451 (0.2%)
Atelectasis	1/446 (0.2%)		0/451 (0%)
Epistaxis	1/446 (0.2%)		0/451 (0%)
Laryngeal oedema	1/446 (0.2%)		0/451 (0%)
Pneumothorax	1/446 (0.2%)		0/451 (0%)
Skin and subcutaneous tissue disorders
Rash macular	0/446 (0%)		1/451 (0.2%)
Rash maculo-papular	0/446 (0%)		1/451 (0.2%)
Toxic epidermal necrolysis	0/446 (0%)		1/451 (0.2%)
Surgical and medical procedures
Fracture treatment	0/446 (0%)		1/451 (0.2%)
Hernia repair	0/446 (0%)		1/451 (0.2%)
Tooth extraction	1/446 (0.2%)		0/451 (0%)
Vascular disorders
Haematoma	0/446 (0%)		2/451 (0.4%)
Hypertension	1/446 (0.2%)		2/451 (0.4%)
Hypotension	1/446 (0.2%)		2/451 (0.4%)
Peripheral ischaemia	0/446 (0%)		1/451 (0.2%)
Aortic disorder	1/446 (0.2%)		0/451 (0%)
Aortic dissection	1/446 (0.2%)		0/451 (0%)
Embolism	1/446 (0.2%)		0/451 (0%)
Peripheral artery aneurysm	1/446 (0.2%)		0/451 (0%)
Shock haemorrhagic	1/446 (0.2%)		0/451 (0%)
Other (Not Including Serious) Adverse Events
	Sunitinib		Atezolizumab + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	433/446 (97.1%)		434/451 (96.2%)
Blood and lymphatic system disorders
Anaemia	91/446 (20.4%)		40/451 (8.9%)
Leukopenia	26/446 (5.8%)		5/451 (1.1%)
Neutropenia	55/446 (12.3%)		3/451 (0.7%)
Thrombocytopenia	78/446 (17.5%)		13/451 (2.9%)
Endocrine disorders
Hyperthyroidism	14/446 (3.1%)		32/451 (7.1%)
Hypothyroidism	111/446 (24.9%)		99/451 (22%)
Gastrointestinal disorders
Abdominal pain	38/446 (8.5%)		40/451 (8.9%)
Abdominal pain upper	36/446 (8.1%)		16/451 (3.5%)
Constipation	62/446 (13.9%)		79/451 (17.5%)
Diarrhoea	230/446 (51.6%)		128/451 (28.4%)
Dry mouth	25/446 (5.6%)		31/451 (6.9%)
Dyspepsia	84/446 (18.8%)		28/451 (6.2%)
Gastrooesophageal reflux disease	51/446 (11.4%)		9/451 (2%)
Stomatitis	99/446 (22.2%)		45/451 (10%)
Toothache	14/446 (3.1%)		25/451 (5.5%)
Vomiting	111/446 (24.9%)		54/451 (12%)
Nausea	167/446 (37.4%)		87/451 (19.3%)
General disorders
Asthenia	103/446 (23.1%)		79/451 (17.5%)
Chest pain	24/446 (5.4%)		15/451 (3.3%)
Fatigue	166/446 (37.2%)		150/451 (33.3%)
Influenza like illness	19/446 (4.3%)		38/451 (8.4%)
Mucosal inflammation	125/446 (28%)		41/451 (9.1%)
Oedema peripheral	45/446 (10.1%)		51/451 (11.3%)
Pain	12/446 (2.7%)		24/451 (5.3%)
Pyrexia	50/446 (11.2%)		69/451 (15.3%)
Infections and infestations
Nasopharyngitis	32/446 (7.2%)		36/451 (8%)
Upper respiratory tract infection	25/446 (5.6%)		33/451 (7.3%)
Urinary tract infection	15/446 (3.4%)		24/451 (5.3%)
Investigations
Alanine aminotransferase increased	34/446 (7.6%)		26/451 (5.8%)
Aspartate aminotransferase increased	35/446 (7.8%)		25/451 (5.5%)
Blood creatinine increased	36/446 (8.1%)		35/451 (7.8%)
Neutrophil count decreased	24/446 (5.4%)		3/451 (0.7%)
Platelet count decreased	46/446 (10.3%)		1/451 (0.2%)
Weight decreased	25/446 (5.6%)		34/451 (7.5%)
Metabolism and nutrition disorders
Decreased appetite	142/446 (31.8%)		83/451 (18.4%)
Hyperkalaemia	13/446 (2.9%)		28/451 (6.2%)
Hyponatraemia	16/446 (3.6%)		25/451 (5.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	56/446 (12.6%)		102/451 (22.6%)
Back pain	55/446 (12.3%)		72/451 (16%)
Musculoskeletal pain	23/446 (5.2%)		40/451 (8.9%)
Myalgia	21/446 (4.7%)		57/451 (12.6%)
Pain in extremity	33/446 (7.4%)		41/451 (9.1%)
Nervous system disorders
Dizziness	24/446 (5.4%)		50/451 (11.1%)
Dysgeusia	128/446 (28.7%)		31/451 (6.9%)
Headache	76/446 (17%)		99/451 (22%)
Psychiatric disorders
Anxiety	15/446 (3.4%)		30/451 (6.7%)
Insomnia	35/446 (7.8%)		35/451 (7.8%)
Renal and urinary disorders
Haematuria	23/446 (5.2%)		12/451 (2.7%)
Proteinuria	29/446 (6.5%)		91/451 (20.2%)
Respiratory, thoracic and mediastinal disorders
Cough	87/446 (19.5%)		96/451 (21.3%)
Dysphonia	18/446 (4%)		61/451 (13.5%)
Dyspnoea	43/446 (9.6%)		56/451 (12.4%)
Epistaxis	65/446 (14.6%)		73/451 (16.2%)
Oropharyngeal pain	16/446 (3.6%)		37/451 (8.2%)
Rhinorrhoea	9/446 (2%)		30/451 (6.7%)
Skin and subcutaneous tissue disorders
Dry skin	37/446 (8.3%)		40/451 (8.9%)
Hair colour changes	31/446 (7%)		0/451 (0%)
Palmar-plantar erythrodysaesthesia syndrome	195/446 (43.7%)		20/451 (4.4%)
Pruritus	30/446 (6.7%)		95/451 (21.1%)
Rash	66/446 (14.8%)		85/451 (18.8%)
Skin discolouration	28/446 (6.3%)		0/451 (0%)
Yellow skin	28/446 (6.3%)		1/451 (0.2%)
Vascular disorders
Hypertension	189/446 (42.4%)		168/451 (37.3%)

Limitations/Caveats

The reported results include data collected up to the clinical data cut-off date of 29 September 2017.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.