IMmotion150: A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) as Monotherapy or in Combination With Bevacizumab (Avastin®) Compared to Sunitinib (Sutent®) in Participants With Untreated Advanced Renal Cell Carcinoma

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01984242
• Collaborator: (none)
• Enrollment: 305
• Locations: 45
• Arms: 3
• Actual Duration (Months): 60
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This multicenter, randomized, open-label study will evaluate the efficacy, safety and tolerability of atezolizumab as monotherapy or in combination with bevacizumab versus sunitinib in participants with histologically confirmed, inoperable, locally advanced or metastatic renal cell carcinoma who have not received prior systemic 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 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 305 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Administered as Monotherapy or in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
• Actual Study Start Date: Jan 8, 2014
• Actual Primary Completion Date: Oct 17, 2016
• Actual Study Completion Date: Jan 8, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atezolizumab and Bevacizumab Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) will be administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.; Other Names: Tecentriq MPDL3280A RO5541267 ; Drug: Bevacizumab; Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.; Other Names: Avastin
Experimental: Atezolizumab Atezolizumab 1200 mg will be administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except European Union [EU] participants) can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.; Other Names: Tecentriq MPDL3280A RO5541267 ; Drug: Bevacizumab; Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.; Other Names: Avastin
Active Comparator: Sunitinib Sunitinib 50 mg will be administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.; Other Names: Tecentriq MPDL3280A RO5541267 ; Drug: Bevacizumab; Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.; Other Names: Avastin ; Drug: Sunitinib; Sunitinib will be administered according to the dosage schedule mentioned in the arm description.; Other Names: Sutent

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   Progressive Disease (PD): at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm); appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

2. Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

3. Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

4. PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

Secondary Outcome Measures

1. Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

2. PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

3. Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

4. PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

5. Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

6. PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

7. Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

8. PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

9. Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

   PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

10. PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

11. Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

12. PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

13. Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to less than (<) 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.

14. Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.

15. Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.

16. Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.

17. Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.

18. Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.

19. Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.

20. PFS Per Modified RECIST Via Investigator Assessment in ITT Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.

21. Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.

22. PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population [From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.

23. Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population [From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.

24. DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population [From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.

25. DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population [From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.

26. DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population [From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.

27. DOR Per Modified RECIST Via Investigator Assessment in ITT Population [From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.

28. DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population [From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.

29. Percentage of Participants Who Died in ITT Population [Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

30. Overall Survival (OS) in ITT Population [Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.

31. Percentage of Participants Who Died in IC1/2/3 Population [Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

32. OS in IC1/2/3 Population [Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.

33. Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population [From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.

34. DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population [From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.

35. Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population [From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

36. PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population [From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)]

    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

37. Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab [Cycle 1 Day 1 until treatment discontinuation (until data cut-off date 17 October 2016, up to approximately 2.75 years) (1 cycle=6 weeks)]

    This outcome measure was planned to be analyzed in 'Atezolizumab' and 'Atezolizumab and Bevacizumab' arms only.

38. Maximum Serum Concentration (Cmax) of Atezolizumab [30 minutes after end of infusion on Cycle 1 Day 1 (1 cycle=6 weeks) (infusion length for first dose=60 minutes)]

39. Minimum Serum Concentration (Cmin) of Atezolizumab [Pre-infusion (0 hour) on Day 1 of Cycles 2 and 4; Day 22 of Cycles 1, 2, and 4 (1 cycle=6 weeks) (infusion length=30-60 minutes)]

40. Cmax of Bevacizumab [30 minutes after end of infusion on Day 1 of Cycles 1 and 2 (1 cycle=6 weeks) (infusion length=30-90 minutes)]

41. Cmin of Bevacizumab [For Atezolizumab and Bevacizumab Arm: at First-line treatment discontinuation (up to approximately 2.75 years); For Crossover Arms: pre-infusion (0 hour) on Day 1 of Cycle 2 (1 cycle=6 weeks) (infusion length=30-90 minutes)]

42. M.D. Anderson Symptom Inventory (MDASI) Interference Score [Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)]

    MDASI questionnaire comprises of 2 parts: symptoms (16 items), interference with daily life (6 items). Participants were asked to rate how much their symptoms interfered with general activity, mood, work, relations with other people, walking, and enjoyment of life during the last 24 hours. Each item in the interference score was answered on a scale of 0 (did not interfere) to 10 (interfered completely). The mean score of all 6 items was reported on the scale of 0 (did not interfere) to 10 (interfered completely).

43. Brief Fatigue Inventory (BFI) Fatigue Level Score [Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)]

    BFI questionnaire comprises of 2 parts: fatigue level (3 items), interference with daily life (1 item with 6 sub-items). Each items in the fatigue level score was answered on a scale of 0 (no fatigue) to 10 (as bad as you can imagine). The mean score of all 3 items was reported on the scale of 0 (no fatigue) to 10 (as bad as you can imagine).

Other Outcome Measures

1. EuroQoL 5 Dimension (EQ-5D) Questionnaire Score [Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)]

   EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Unresectable advanced or metastatic renal cell carcinoma with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agents, including treatment in the adjuvant setting

• Measurable disease, as defined by RECIST v1.1

• Karnofsky performance score greater than or equal to (>/=) 70

• Adequate hematologic and end-organ function as defined by protocol

• Women of childbearing potential and male participants with partners of childbearing potential must agree to use highly effective methods of contraception as defined by protocol

Exclusion Criteria:

Disease-Specific Exclusions:

• Radiotherapy for renal cell carcinoma within 14 days prior to Cycle 1, Day 1 with the exception of single-fraction radiotherapy given for the indication of pain control

• Known active malignancies or metastasis of the brain or spinal cord or leptomeningeal disease, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)

• Uncontrolled hypercalcemia or symptomatic hypercalcemia

• Malignancies other than renal cell carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death, treated with expected curative outcome

General Medical Exclusions:

• Life expectancy of less than (<) 12 weeks

• Pregnant and lactating women

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

• History of autoimmune disease

• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan

• Participants with active or chronic hepatitis B, active hepatitis C, Human Immunodeficiency Virus (HIV) positive test, significant cardiovascular disease

• Prior allogeneic stem cell or solid organ transplant

Exclusion Criteria Related to Medications:

• Prior treatment with Cluster of Differentiation 137 (CD137) agonists, anti-Cytotoxic T-Lymphocyte Antigen-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents

• Treatment with systemic immunostimulatory agents for any reason within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1

• Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1

Bevacizumab- and Sunitinib-Specific Exclusions:

• Inadequately controlled hypertension

• Prior history of hypertensive crisis or hypertensive encephalopathy

• New York Heart Association Class II or greater congestive heart failure

• History of myocardial infarction or unstable angina, stroke or transient ischemic attack within 3 months prior to Cycle 1, Day 1

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth Research Institute - Bisgrove	Scottsdale	Arizona	United States	85258
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
3	UCLA	Los Angeles	California	United States	90024
4	University of California	San Francisco	California	United States	94158
5	Univ Colorado Health Sci Ctr	Aurora	Colorado	United States	80045
6	Rocky Mountain Cancer Ctr - Denver (Williams)	Denver	Colorado	United States	80218
7	Yale Uni School of Medicine; Section of Medical Oncology	New Haven	Connecticut	United States	06510-3289
8	Georgetown U; Lombardi Comp Can	Washington	District of Columbia	United States	20016-1468
9	SCRI Florida Cancer Specialists South	Fort Myers	Florida	United States	33916
10	Mayo Clinic-Jacksonville	Jacksonville	Florida	United States	32224
11	Florida Cancer Specialist, North Region	Saint Petersburg	Florida	United States	33705
12	The University of Chicago	Chicago	Illinois	United States	60637
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	Karmanos Cancer Institute.	Detroit	Michigan	United States	48201
17	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89128
18	Memorial Sloan-Kettering	New York	New York	United States
19	Oncology Hematology Care Inc	Cincinnati	Ohio	United States	45242
20	Cleveland Clinic Foundation; Taussig Cancer Center	Cleveland	Ohio	United States	44195
21	Oncology Associates of Oregon, P.C	Eugene	Oregon	United States	97401
22	Northwest Cancer Specialists, P.C.	Tigard	Oregon	United States	97223
23	Tennessee Oncology PLLC - Nashville (20th Ave)	Nashville	Tennessee	United States	37203
24	Vanderbilt Medical Center	Nashville	Tennessee	United States	37232-7610
25	Texas Oncology-Baylor Sammons Cancer Center	Dallas	Texas	United States	75246
26	Fakultni nemocnice Olomouc	Olomouc		Czechia	775 20
27	Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale	Paris		France	75908
28	CHU Bordeaux	Pessac		France	33604
29	Institut Gustave Roussy; Departement Oncologie Medicale	Villejuif		France	94805
30	Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie	Hannover		Germany	30625
31	Klinikum rechts der Isar der TU München; Klinikapotheke	Muenchen		Germany	81675
32	Klinikum d.Universität München Campus Großhadern	München		Germany	81377
33	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2	Milano	Lombardia	Italy	20133
34	Medical Oncology, Arezzo	Arezzo	Toscana	Italy	52100
35	Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica	Siena	Toscana	Italy	53100
36	Centrum Med. Ostrobramska NZOZ Magodent	Warszawa		Poland	04-125
37	Prof. Dr. I. Chiricuta Institute of Oncology	Cluj Napoca		Romania	400015
38	Medisprof SRL	Cluj-Napoca		Romania	400058
39	Clinica Universitaria de Navarra	Pamplona	Navarra	Spain	31008
40	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
41	Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department	Barcelona		Spain	08036
42	Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal	Madrid		Spain	28050
43	Barts and the London NHS Trust.	London		United Kingdom	EC1A 7BE
44	Royal Marsden Hospital - London	London		United Kingdom	SW3 6JJ
45	Christie Hospital Nhs Trust; Medical Oncology	Manchester		United Kingdom	M2O 4BX

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01984242
• Other Study ID Numbers: WO29074; 2013-003167-58
• First Posted: Nov 14, 2013
• Last Update Posted: Dec 23, 2019
• Last Verified: Dec 1, 2019

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

Study Results

Participant Flow

Pre-assignment Detail	Total 305 participants enrolled in this study. Participants enrolled in atezolizumab (except European Union [EU] participants) or sunitinib group could crossover to receive atezolizumab and bevacizumab combination therapy in case of disease progression. Some participants didn't complete due to study termination, but study was completed as planned.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Period Title: Overall Study
STARTED	101	103	101
Treated	101	103	100
COMPLETED	0	0	0
NOT COMPLETED	101	103	101

Baseline Characteristics

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib	Total
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Total of all reporting groups
Overall Participants	101	103	101	305
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.1 (10.8)	60.1 (10.2)	59.7 (10.8)	60.3 (10.6)
Sex: Female, Male (Count of Participants)
Female	27 26.7%	26 25.2%	22 21.8%	75 24.6%
Male	74 73.3%	77 74.8%	79 78.2%	230 75.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population
Description	Progressive Disease (PD): at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm); appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	101	103	101
Number [percentage of participants]	66.3 65.6%	59.2 57.5%	58.4 57.8%

2. Primary Outcome

Title	Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population
Description	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	101	103	101
Median (95% Confidence Interval) [months]	11.7	6.1	8.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9819
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3580
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population
Description	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population included ITT participants with programmed death-ligand 1 (PD-L1) expression of greater than or equal to (>=) 1% on tumor-infiltrating immune cells.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	50	54	60
Number [percentage of participants]	58.0 57.4%	59.3 57.6%	68.3 67.6%

4. Primary Outcome

Title	PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
Description	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	50	54	60
Median (95% Confidence Interval) [months]	14.7	5.5	7.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0952
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.64
	Confidence Interval	() 95%; 0.38 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9172
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.63 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
Description	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Biomarker evaluable population included ITT participants whose tumor samples had sufficient material available for gene signature expression analyses. Participants with higher than median expression of an immune gene signature were included in this analysis.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	45	44	42
Number [percentage of participants]	55.6 55%	61.4 59.6%	73.8 73.1%

6. Secondary Outcome

Title	PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
Description	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Biomarker evaluable population. Participants with higher than median expression of an immune gene signature were included in this analysis.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	45	44	42
Median (95% Confidence Interval) [months]	17.5	5.7	7.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0153
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.48
	Confidence Interval	(2-Sided) 95%; 0.26 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5545
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
Description	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Biomarker evaluable population. Participants with higher than median expression of an immune gene signature were included in this analysis.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	45	44	42
Number [percentage of participants]	57.8 57.2%	77.3 75%	83.3 82.5%

8. Secondary Outcome

Title	PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
Description	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Biomarker evaluable population. Participants with higher than median expression of an immune gene signature were included in this analysis.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	45	44	42
Median (95% Confidence Interval) [months]	16.6	5.5	6.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0086
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; 0.28 to 0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7675
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	() 95%; 0.56 to 1.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
Description	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	61	55	60
Number [percentage of participants]	59.0 58.4%	58.2 56.5%	65.0 64.4%

10. Secondary Outcome

Title	PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
Description	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	61	55	60
Median (95% Confidence Interval) [months]	13.8	5.7	8.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1973
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	() 95%; 0.44 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7738
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
Description	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	61	55	60
Number [percentage of participants]	63.9 63.3%	76.4 74.2%	78.3 77.5%

12. Secondary Outcome

Title	PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
Description	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	61	55	60
Median (95% Confidence Interval) [months]	11.1	5.5	7.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0830
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.68
	Confidence Interval	() 95%; 0.43 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7141
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population
Description	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	101	103	101
Number [percentage of participants]	71.3 70.6%	75.7 73.5%	75.2 74.5%

14. Secondary Outcome

Title	PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population
Description	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	101	103	101
Median (95% Confidence Interval) [months]	11.1	5.5	7.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2541
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	() 95%; 0.59 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3103
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population
Description	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	50	54	60
Number [percentage of participants]	66.0 65.3%	74.1 71.9%	81.7 80.9%

16. Secondary Outcome

Title	PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
Description	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	50	54	60
Median (95% Confidence Interval) [months]	11.1	5.5	7.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0351
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9769
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	() 95%; 0.64 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population
Description	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to less than (<) 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	101	103	101
Number (95% Confidence Interval) [percentage of participants]	31.7 31.4%	25.2 24.5%	28.7 28.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6492
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	2.97
	Confidence Interval	(2-Sided) 95%; -10.68 to 16.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5433
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-3.47
	Confidence Interval	() 95%; -16.63 to 9.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
Description	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	50	54	60
Number (95% Confidence Interval) [percentage of participants]	46.0 45.5%	27.8 27%	26.7 26.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0141
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	19.33
	Confidence Interval	(2-Sided) 95%; -0.28 to 38.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8719
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; -17.02 to 19.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population
Description	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	101	103	101
Number (95% Confidence Interval) [percentage of participants]	34.7 34.4%	23.3 22.6%	32.7 32.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8068
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	1.98
	Confidence Interval	(2-Sided) 95%; -12.04 to 16.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1321
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-9.37
	Confidence Interval	() 95%; -22.61 to 3.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
Description	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	50	54	60
Number (95% Confidence Interval) [percentage of participants]	48.0 47.5%	25.9 25.1%	28.3 28%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0199
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	19.67
	Confidence Interval	(2-Sided) 95%; -0.10 to 39.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7836
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-2.41
	Confidence Interval	(2-Sided) 95%; -20.50 to 15.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population
Description	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	101	103	101
Number (95% Confidence Interval) [percentage of participants]	37.6 37.2%	25.2 24.5%	33.7 33.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6231
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	3.96
	Confidence Interval	(2-Sided) 95%; -10.23 to 18.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1816
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-8.42
	Confidence Interval	(2-Sided) 95%; -21.86 to 5.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
Description	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	50	54	60
Number (95% Confidence Interval) [percentage of participants]	52.0 51.5%	27.8 27%	30.0 29.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0111
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	22.00
	Confidence Interval	(2-Sided) 95%; 2.11 to 41.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8209
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-2.22
	Confidence Interval	(2-Sided) 95%; -20.63 to 16.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population
Description	PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	101	103	101
Number [percentage of participants]	60.4 59.8%	61.2 59.4%	63.4 62.8%

24. Secondary Outcome

Title	PFS Per Modified RECIST Via Investigator Assessment in ITT Population
Description	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	101	103	101
Median (95% Confidence Interval) [months]	16.7	10.9	9.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0863
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	() 95%; 0.50 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5922
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population
Description	PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	50	54	60
Number [percentage of participants]	52.0 51.5%	59.3 57.6%	75.0 74.3%

26. Secondary Outcome

Title	PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
Description	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.
Time Frame	From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	50	54	60
Median (95% Confidence Interval) [months]	21.7	10.9	8.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.43
	Confidence Interval	() 95%; 0.25 to 0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6566
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.56 to 1.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population
Description	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Time Frame	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	32	26	29
Median (95% Confidence Interval) [months]	22.1	NA	NA

28. Secondary Outcome

Title	DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population
Description	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Time Frame	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	35	24	33
Median (95% Confidence Interval) [months]	NA	NA	14.2

29. Secondary Outcome

Title	DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
Description	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Time Frame	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	23	15	16
Median (95% Confidence Interval) [months]	22.1	NA	NA

30. Secondary Outcome

Title	DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
Description	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Time Frame	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	24	14	17
Median (95% Confidence Interval) [months]	22.4	NA	14.1

31. Secondary Outcome

Title	DOR Per Modified RECIST Via Investigator Assessment in ITT Population
Description	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.
Time Frame	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	38	26	34
Median (95% Confidence Interval) [months]	NA	NA	16.6

32. Secondary Outcome

Title	DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
Description	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.
Time Frame	From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	26	15	18
Median (95% Confidence Interval) [months]	22.4	NA	16.6

33. Secondary Outcome

Title	Percentage of Participants Who Died in ITT Population
Time Frame	Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	101	103	101
Number [percentage of participants]	38.6 38.2%	35.0 34%	30.7 30.4%

34. Secondary Outcome

Title	Overall Survival (OS) in ITT Population
Description	OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.
Time Frame	Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	101	103	101
Median (95% Confidence Interval) [months]	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2867
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 95%; 0.80 to 2.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8039
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	() 95%; 0.65 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

35. Secondary Outcome

Title	Percentage of Participants Who Died in IC1/2/3 Population
Time Frame	Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	50	54	60
Number [percentage of participants]	38.0 37.6%	39.8 38.6%	35.0 34.7%

36. Secondary Outcome

Title	OS in IC1/2/3 Population
Description	OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.
Time Frame	Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

IC1/2/3 population

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	50	54	60
Median (95% Confidence Interval) [months]	27.3	30.2	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab and Bevacizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7879
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.47 to 1.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab, Sunitinib
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9065
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

37. Secondary Outcome

Title	Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population
Description	Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Time Frame	From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Crossover population included participants in atezolizumab or sunitinib arms who had crossed over to the atezolizumab and bevacizumab arm. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab (Crossover)	Sunitinib (Crossover)
Arm/Group Description	Among the participants assigned to atezolizumab initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.	Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
Measure Participants	41	54
Number (95% Confidence Interval) [percentage of participants]	24.4 24.2%	27.8 27%

38. Secondary Outcome

Title	DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population
Description	DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Time Frame	From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Crossover population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab (Crossover)	Sunitinib (Crossover)
Arm/Group Description	Among the participants assigned to atezolizumab initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.	Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
Measure Participants	10	15
Median (95% Confidence Interval) [months]	NA	NA

39. Secondary Outcome

Title	Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population
Description	PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time Frame	From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Crossover population

Arm/Group Title	Atezolizumab (Crossover)	Sunitinib (Crossover)
Arm/Group Description	Among the participants assigned to atezolizumab initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.	Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
Measure Participants	44	57
Number [percentage of participants]	59.1 58.5%	68.4 66.4%

40. Secondary Outcome

Title	PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population
Description	PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time Frame	From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Outcome Measure Data

Analysis Population Description

Crossover population

Arm/Group Title	Atezolizumab (Crossover)	Sunitinib (Crossover)
Arm/Group Description	Among the participants assigned to atezolizumab initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.	Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
Measure Participants	44	57
Median (95% Confidence Interval) [months]	12.6	8.3

41. Secondary Outcome

Title	Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab
Description	This outcome measure was planned to be analyzed in 'Atezolizumab' and 'Atezolizumab and Bevacizumab' arms only.
Time Frame	Cycle 1 Day 1 until treatment discontinuation (until data cut-off date 17 October 2016, up to approximately 2.75 years) (1 cycle=6 weeks)

Outcome Measure Data

Analysis Population Description

ATA evaluable population included participants at baseline who had a baseline ATA sample and post-baseline participants who had at least one ATA sample and had received at least one dose of study treatment.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	97	96
Number [percentage of participants]	34.0 33.7%	25.0 24.3%

42. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) of Atezolizumab
Time Frame	30 minutes after end of infusion on Cycle 1 Day 1 (1 cycle=6 weeks) (infusion length for first dose=60 minutes)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) evaluable population included participants who received at least one dose of study drug and had sufficient PK sample collected within the time specified in the protocol. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Atezolizumab (Crossover)	Sunitinib (Crossover)
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Among the participants assigned to atezolizumab initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.	Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
Measure Participants	95	93	41	53
Mean (Standard Deviation) [micrograms per milliliter (mcg/mL)]	335 (86.0)	358 (93.1)	418 (114)	314 (87.1)

43. Secondary Outcome

Title	Minimum Serum Concentration (Cmin) of Atezolizumab
Time Frame	Pre-infusion (0 hour) on Day 1 of Cycles 2 and 4; Day 22 of Cycles 1, 2, and 4 (1 cycle=6 weeks) (infusion length=30-60 minutes)

Outcome Measure Data

Analysis Population Description

PK evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure. 'Number Analyzed'=participants evaluable for this outcome measure at specified timepoint for each arm respectively.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Atezolizumab (Crossover)	Sunitinib (Crossover)
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Among the participants assigned to atezolizumab initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.	Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
Measure Participants	98	94	42	52
Cycle 1 Day 22	72.6 (29.5)	79.9 (26.1)	174 (121)	73.2 (31.5)
Cycle 2 Day 1	122 (50.4)	125 (47.4)	158 (101)	106 (45.2)
Cycle 2 Day 22	152 (65.3)	159 (84.6)	164 (70.7)	141 (85.5)
Cycle 4 Day 1	183 (90.5)	192 (77.6)	154 (62.7)	174 (75.7)
Cycle 4 Day 22	190 (86.3)	200 (90.0)	163 (70.5)	172 (78.8)

44. Secondary Outcome

Title	Cmax of Bevacizumab
Time Frame	30 minutes after end of infusion on Day 1 of Cycles 1 and 2 (1 cycle=6 weeks) (infusion length=30-90 minutes)

Outcome Measure Data

Analysis Population Description

PK evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab (Crossover)	Sunitinib (Crossover)
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Among the participants assigned to atezolizumab initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.	Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
Measure Participants	86	34	44
Mean (Standard Deviation) [mcg/mL]	89.8 (39.4)	433 (115)	455 (106)

45. Secondary Outcome

Title	Cmin of Bevacizumab
Time Frame	For Atezolizumab and Bevacizumab Arm: at First-line treatment discontinuation (up to approximately 2.75 years); For Crossover Arms: pre-infusion (0 hour) on Day 1 of Cycle 2 (1 cycle=6 weeks) (infusion length=30-90 minutes)

Outcome Measure Data

Analysis Population Description

PK evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab (Crossover)	Sunitinib (Crossover)
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Among the participants assigned to atezolizumab initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.	Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
Measure Participants	42	39	42
Mean (Standard Deviation) [mcg/mL]	75.2 (72.1)	101 (48.7)	95.9 (43.9)

46. Secondary Outcome

Title	M.D. Anderson Symptom Inventory (MDASI) Interference Score
Description	MDASI questionnaire comprises of 2 parts: symptoms (16 items), interference with daily life (6 items). Participants were asked to rate how much their symptoms interfered with general activity, mood, work, relations with other people, walking, and enjoyment of life during the last 24 hours. Each item in the interference score was answered on a scale of 0 (did not interfere) to 10 (interfered completely). The mean score of all 6 items was reported on the scale of 0 (did not interfere) to 10 (interfered completely).
Time Frame	Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)

Outcome Measure Data

Analysis Population Description

Patient Reported Outcome (PRO)-evaluable population: randomized participants who had non-missing baseline assessment and at least 1 post-baseline assessment. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome. 'Number Analyzed'=participants evaluable for this outcome at specified timepoint for each arm, respectively.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	96	95	93
Cycle 1 Day 1	1.60 (1.97)	1.38 (2.03)	1.79 (2.39)
Cycle 1 Day 22	2.08 (2.34)	1.26 (2.07)	3.16 (2.65)
Cycle 2 Day 1	1.56 (1.82)	1.20 (1.72)	1.83 (2.19)
Cycle 2 Day 22	1.57 (1.83)	1.04 (1.62)	2.50 (2.47)
Cycle 3 Day 1	1.72 (2.15)	0.90 (1.43)	1.49 (2.01)
Cycle 3 Day 22	1.66 (2.07)	1.01 (1.58)	2.20 (2.42)
Cycle 4 Day 1	1.59 (2.11)	1.24 (1.99)	1.61 (2.24)
Cycle 4 Day 22	1.68 (2.31)	1.26 (1.98)	1.92 (2.00)
Cycle 5 Day 1	1.70 (2.29)	0.69 (1.11)	1.53 (1.96)
Cycle 5 Day 22	1.80 (2.29)	0.67 (1.33)	1.97 (2.21)
Cycle 6 Day 1	1.91 (2.54)	0.64 (1.13)	1.39 (1.76)
Cycle 6 Day 22	1.80 (2.38)	0.63 (1.12)	2.00 (2.23)
Cycle 7 Day 1	1.99 (2.49)	0.53 (0.78)	1.00 (1.09)
Cycle 7 Day 22	2.01 (2.45)	0.59 (0.93)	1.15 (1.04)
Cycle 8 Day 1	1.88 (2.26)	0.55 (0.85)	0.94 (1.04)
Cycle 8 Day 22	1.81 (2.41)	0.58 (0.91)	1.34 (1.39)
Cycle 9 Day 1	1.75 (2.24)	0.55 (0.90)	1.16 (1.22)
Cycle 9 Day 22	1.64 (2.16)	0.58 (0.89)	1.57 (1.61)
Cycle 10 Day 1	1.43 (1.82)	0.81 (1.13)	1.08 (1.40)
Cycle 10 Day 22	1.55 (2.09)	0.70 (1.10)	1.49 (1.78)
Cycle 11 Day 1	1.65 (2.13)	0.61 (0.95)	0.98 (1.00)
Cycle 11 Day 22	1.35 (1.81)	0.78 (1.07)	1.47 (1.61)
Cycle 12 Day 1	1.21 (1.69)	0.68 (1.15)	0.84 (0.83)
Cycle 12 Day 22	1.51 (2.23)	0.53 (0.99)	1.41 (1.53)
Cycle 13 Day 1	1.50 (2.16)	0.68 (1.07)	1.26 (1.45)
Cycle 13 Day 22	1.45 (2.32)	0.67 (1.10)	1.32 (1.37)
Cycle 14 Day 1	1.60 (2.24)	0.67 (0.95)	1.07 (1.31)
Cycle 14 Day 22	1.40 (2.09)	0.63 (0.94)	1.50 (1.48)
Cycle 15 Day 1	1.16 (1.74)	0.84 (1.16)	1.50 (1.64)
Cycle 15 Day 22	1.48 (1.92)	0.71 (1.10)	2.08 (1.64)
Cycle 16 Day 1	0.87 (0.99)	0.85 (1.40)	1.07 (1.22)
Cycle 16 Day 22	0.72 (0.93)	0.87 (1.30)	2.04 (2.24)
Cycle 17 Day 1	0.98 (0.99)	0.57 (0.75)	0.71 (0.95)
Cycle 17 Day 22	0.73 (1.02)	0.65 (0.97)	1.21 (1.32)
Cycle 18 Day 1	0.93 (1.07)	0.71 (0.98)	0.95 (1.15)
Cycle 18 Day 22	0.79 (1.06)	0.33 (0.41)	1.05 (1.42)
Cycle 19 Day 1	1.11 (1.25)	0.31 (0.34)	1.33 (1.66)
Cycle 19 Day 22	0.97 (1.37)	0.30 (0.41)	1.55 (1.69)
Cycle 20 Day 1	1.19 (1.31)	0.21 (0.42)	0.90 (1.07)
Cycle 20 Day 22	1.10 (1.30)	0.04 (0.08)	1.67 (1.56)
Cycle 21 Day 1	1.17 (1.42)	0.00 (0.00)	0.78 (1.07)
Cycle 21 Day 22	1.23 (1.51)	0.00 (NA)	1.25 (1.53)
Cycle 22 Day 1	0.54 (0.76)	0.00 (NA)	0.83 (0.71)
Cycle 22 Day 22	0.94 (1.07)	0.00 (NA)	1.25 (1.53)
Cycle 23 Day 1	1.67 (1.89)	0.00 (NA)	1.58 (2.00)
Cycle 23 Day 22	1.25 (1.77)	0.00 (NA)	2.67 (2.36)
Cycle 24 Day 1	2.33 (NA)	0.00 (NA)	1.67 (NA)
Cycle 24 Day 22	0.00 (NA)	0.50 (NA)
Cycle 25 Day 1	0.00 (NA)
Treatment discontinuation	2.54 (2.66)	2.29 (2.54)	3.49 (3.16)

47. Secondary Outcome

Title	Brief Fatigue Inventory (BFI) Fatigue Level Score
Description	BFI questionnaire comprises of 2 parts: fatigue level (3 items), interference with daily life (1 item with 6 sub-items). Each items in the fatigue level score was answered on a scale of 0 (no fatigue) to 10 (as bad as you can imagine). The mean score of all 3 items was reported on the scale of 0 (no fatigue) to 10 (as bad as you can imagine).
Time Frame	Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)

Outcome Measure Data

Analysis Population Description

PRO-evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure. 'Number Analyzed'=participants evaluable for this outcome measure at specified timepoint for each arm respectively.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	95	94	93
Cycle 1 Day 1	2.80 (2.64)	2.52 (2.72)	2.66 (2.74)
Cycle 1 Day 22	3.80 (2.86)	2.55 (2.60)	4.42 (3.09)
Cycle 2 Day 1	3.21 (2.61)	2.63 (2.69)	2.86 (2.76)
Cycle 2 Day 22	3.15 (2.61)	2.57 (2.74)	3.69 (2.74)
Cycle 3 Day 1	2.91 (2.60)	2.11 (2.42)	2.35 (2.44)
Cycle 3 Day 22	2.93 (2.67)	2.31 (2.71)	3.60 (3.09)
Cycle 4 Day 1	3.21 (2.66)	2.32 (2.86)	2.39 (2.47)
Cycle 4 Day 22	3.06 (2.68)	2.33 (2.94)	3.15 (2.57)
Cycle 5 Day 1	2.97 (2.83)	1.59 (2.03)	2.32 (2.62)
Cycle 5 Day 22	3.02 (2.87)	1.34 (1.81)	2.91 (2.86)
Cycle 6 Day 1	3.05 (2.83)	1.42 (1.90)	2.22 (2.48)
Cycle 6 Day 22	3.23 (2.94)	1.39 (2.01)	3.09 (2.69)
Cycle 7 Day 1	3.16 (2.81)	1.33 (1.91)	1.68 (1.75)
Cycle 7 Day 22	2.86 (2.60)	1.24 (1.67)	2.16 (1.87)
Cycle 8 Day 1	2.80 (2.56)	1.12 (1.68)	1.72 (1.70)
Cycle 8 Day 22	2.88 (2.80)	1.24 (1.75)	2.58 (2.13)
Cycle 9 Day 1	3.09 (2.81)	1.11 (1.55)	2.12 (2.48)
Cycle 9 Day 22	2.80 (2.73)	1.19 (1.71)	2.64 (2.57)
Cycle 10 Day 1	2.80 (2.58)	1.29 (1.88)	2.11 (2.23)
Cycle 10 Day 22	2.91 (2.83)	1.33 (1.90)	2.24 (2.43)
Cycle 11 Day 1	2.98 (2.71)	1.40 (1.96)	1.93 (1.65)
Cycle 11 Day 22	2.59 (2.44)	1.72 (2.23)	2.42 (2.12)
Cycle 12 Day 1	2.31 (2.25)	1.25 (1.96)	1.66 (1.67)
Cycle 12 Day 22	2.79 (2.46)	1.44 (2.12)	2.27 (2.05)
Cycle 13 Day 1	2.69 (2.57)	1.65 (2.17)	2.08 (1.56)
Cycle 13 Day 22	2.97 (2.97)	1.55 (2.13)	2.60 (2.28)
Cycle 14 Day 1	2.94 (2.94)	1.45 (2.14)	2.30 (2.34)
Cycle 14 Day 22	2.83 (2.85)	1.61 (2.00)	2.60 (2.09)
Cycle 15 Day 1	2.73 (2.56)	1.76 (2.19)	2.60 (2.33)
Cycle 15 Day 22	2.61 (2.79)	0.92 (1.12)	2.94 (1.61)
Cycle 16 Day 1	1.88 (1.99)	1.54 (2.07)	2.21 (2.42)
Cycle 16 Day 22	1.70 (1.61)	2.11 (2.15)	2.85 (2.19)
Cycle 17 Day 1	1.78 (1.59)	1.60 (1.96)	1.50 (1.51)
Cycle 17 Day 22	2.00 (1.80)	2.13 (2.42)	2.38 (1.60)
Cycle 18 Day 1	2.23 (1.74)	1.88 (2.23)	1.71 (1.70)
Cycle 18 Day 22	1.92 (2.14)	1.67 (2.07)	2.14 (2.19)
Cycle 19 Day 1	2.17 (2.48)	1.50 (1.97)	2.29 (3.30)
Cycle 19 Day 22	1.90 (2.42)	1.40 (2.19)	3.29 (2.43)
Cycle 20 Day 1	3.00 (3.16)	1.25 (2.50)	1.80 (1.30)
Cycle 20 Day 22	2.40 (3.05)	1.50 (3.00)	2.25 (2.06)
Cycle 21 Day 1	2.60 (2.97)	2.50 (3.54)	1.67 (1.53)
Cycle 21 Day 22	2.40 (1.95)	0.00 (NA)	2.00 (1.41)
Cycle 22 Day 1	1.25 (1.89)	0.00 (NA)	2.00 (1.41)
Cycle 22 Day 22	1.33 (2.31)	0.00 (NA)	3.00 (2.83)
Cycle 23 Day 1	2.50 (3.54)	0.00 (NA)	2.00 (2.83)
Cycle 23 Day 22	2.00 (2.83)	0.00 (NA)	4.50 (3.54)
Cycle 24 Day 1	4.00 (NA)	0.00 (NA)	2.00 (NA)
Cycle 24 Day 22	0.00 (NA)	0.00 (NA)
Cycle 25 Day 1	0.00 (NA)
Treatment discontinuation	3.74 (2.82)	3.95 (3.27)	3.75 (3.09)

48. Other Pre-specified Outcome

Title	EuroQoL 5 Dimension (EQ-5D) Questionnaire Score
Description	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Time Frame	Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)

Outcome Measure Data

Analysis Population Description

As this outcome was pre-specified as an exploratory outcome, no results are reported.

Arm/Group Title	Atezolizumab and Bevacizumab	Atezolizumab	Sunitinib
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.	Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.	Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Measure Participants	0	0	0

Adverse Events

Time Frame	Baseline up to approximately 60 months.
Adverse Event Reporting Description	Safety-evaluable population included all participants who received at least one dose of any study medication. Adverse events were reported separately for crossed over participants.
Arm/Group Title	Atezolizumab and Bevacizumab		Atezolizumab		Sunitinib		Atezolizumab (Crossover)		Sunitinib (Crossover)
Arm/Group Description	Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.		Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.		Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.		Among the participants assigned to atezolizumab initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.		Among the participants assigned to sunitinib initially, those participants who upon disease progression, crossed over to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination, were included in this group. Atezolizumab 1200 mg and bevacizumab 15 mg/kg were administered as IV infusions q3w on Day 1 and Day 22 of each 6-week cycle.
All Cause Mortality
	Atezolizumab and Bevacizumab		Atezolizumab		Sunitinib		Atezolizumab (Crossover)		Sunitinib (Crossover)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Atezolizumab and Bevacizumab		Atezolizumab		Sunitinib		Atezolizumab (Crossover)		Sunitinib (Crossover)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/101 (48.5%)		37/103 (35.9%)		28/100 (28%)		15/46 (32.6%)		22/63 (34.9%)
Blood and lymphatic system disorders
Anaemia	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Febrile neutropenia	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Cardiac disorders
Angina pectoris	2/101 (2%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Atrial fibrillation	1/101 (1%)		1/103 (1%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Cardiac failure congestive	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Cardiomyopathy	0/101 (0%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Myocardial infarction	1/101 (1%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Tachycardia	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Ear and labyrinth disorders
Vertigo	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Endocrine disorders
Adrenal insufficiency	1/101 (1%)		0/103 (0%)		0/100 (0%)		2/46 (4.3%)		0/63 (0%)
Gastrointestinal disorders
Abdominal pain	1/101 (1%)		1/103 (1%)		0/100 (0%)		1/46 (2.2%)		2/63 (3.2%)
Ascites	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Autoimmune pancreatitis	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Constipation	0/101 (0%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		2/63 (3.2%)
Diarrhoea	4/101 (4%)		0/103 (0%)		2/100 (2%)		0/46 (0%)		0/63 (0%)
Gastritis	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Gastrointestinal haemorrhage	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Gastrointestinal inflammation	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Gastrooesophageal reflux disease	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Intestinal haemorrhage	0/101 (0%)		1/103 (1%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Intestinal obstruction	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Mesenteric vein thrombosis	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Nausea	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		3/63 (4.8%)
Pancreatic fistula	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		1/63 (1.6%)
Pancreatitis	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Pancreatitis acute	0/101 (0%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Peritoneal haemorrhage	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Rectal haemorrhage	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Retroperitoneal haemorrhage	1/101 (1%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Small intestinal obstruction	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Vomiting	1/101 (1%)		1/103 (1%)		1/100 (1%)		0/46 (0%)		2/63 (3.2%)
Colitis microscopic	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Obstructive pancreatitis	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
General disorders
Chest pain	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Fatigue	0/101 (0%)		1/103 (1%)		1/100 (1%)		1/46 (2.2%)		1/63 (1.6%)
General physical health deterioration	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Mucosal inflammation	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Non-cardiac chest pain	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		1/63 (1.6%)
Pain	1/101 (1%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		3/63 (4.8%)
Pyrexia	2/101 (2%)		4/103 (3.9%)		2/100 (2%)		0/46 (0%)		2/63 (3.2%)
Sudden death	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Asthenia	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Death	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Oedema	0/101 (0%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Hepatobiliary disorders
Bile duct stenosis	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Cholecystitis	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Cholelithiasis	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Hepatorenal syndrome	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Hyperbilirubinaemia	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Immune system disorders
Haemophagocytic lymphohistiocytosis	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Infections and infestations
Appendicitis	0/101 (0%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Arthritis infective	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Bacteraemia	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Bronchitis	1/101 (1%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Cellulitis	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Chest wall abscess	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Diverticulitis	3/101 (3%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Gastroenteritis	2/101 (2%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Influenza	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Lower respiratory tract infection	0/101 (0%)		3/103 (2.9%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Meningitis viral	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Necrotising fasciitis	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Pancreatic abscess	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Paronychia	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Peritonitis bacterial	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Pneumonia	3/101 (3%)		2/103 (1.9%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Sinusitis	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Spinal cord infection	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Staphylococcal infection	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Urinary tract infection	1/101 (1%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Wound infection	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Abscess	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Biliary sepsis	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Osteomyelitis	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Psoas abscess	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Sepsis	1/101 (1%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Skin infection	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Injury, poisoning and procedural complications
Fall	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Hip fracture	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Incisional hernia	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Infusion related reaction	0/101 (0%)		2/103 (1.9%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Spinal compression fracture	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Femur fracture	1/101 (1%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Investigations
Blood creatinine increased	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Alanine aminotransferase increased	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Asparate aminotransferase increased	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Blood bilirubin increased	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Metabolism and nutrition disorders
Decreased appetite	1/101 (1%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Dehydration	2/101 (2%)		1/103 (1%)		2/100 (2%)		0/46 (0%)		0/63 (0%)
Diabetes mellitus	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Hypercalcaemia	0/101 (0%)		2/103 (1.9%)		0/100 (0%)		0/46 (0%)		3/63 (4.8%)
Hyperglycaemia	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Hyperkalaemia	0/101 (0%)		0/103 (0%)		2/100 (2%)		0/46 (0%)		1/63 (1.6%)
Hyponatraemia	4/101 (4%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/101 (1%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		5/63 (7.9%)
Bone pain	0/101 (0%)		0/103 (0%)		2/100 (2%)		0/46 (0%)		1/63 (1.6%)
Chondrocalcinosis	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Flank pain	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Fracture pain	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Muscle haemorrhage	0/101 (0%)		0/103 (0%)		1/100 (1%)		1/46 (2.2%)		0/63 (0%)
Musculoskeletal pain	0/101 (0%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Neck pain	0/101 (0%)		0/103 (0%)		0/100 (0%)		2/46 (4.3%)		0/63 (0%)
Neuropathic arthropathy	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Pain in extremity	0/101 (0%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Pathological fracture	2/101 (2%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial tumour haemorrhage	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Squamous cell carcinoma of skin	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Metastases to central nervous system	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Nervous system disorders
Amnesia	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Autoimmune neuropathy	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Demyelination	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Facial paralysis	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Haemorrhage intracranial	1/101 (1%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Headache	2/101 (2%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Hemiparesis	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Nerve root compression	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Peripheral sensorimotor neuropathy	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Spinal cord compression	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Syncope	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Cerebrovascular accident	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Intracranial haematoma	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Paresis	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Psychiatric disorders
Confusional state	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Depression	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Mental status changes	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Renal and urinary disorders
Acute kidney injury	1/101 (1%)		3/103 (2.9%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Haematuria	3/101 (3%)		2/103 (1.9%)		1/100 (1%)		2/46 (4.3%)		0/63 (0%)
Renal failure	0/101 (0%)		1/103 (1%)		2/100 (2%)		0/46 (0%)		0/63 (0%)
Urethral stenosis	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Chronic obstructive pulmonary disease	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Dyspnoea	1/101 (1%)		4/103 (3.9%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Haemoptysis	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Hypoxia	1/101 (1%)		1/103 (1%)		2/100 (2%)		0/46 (0%)		0/63 (0%)
Laryngeal mass	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Obstructive airways disorder	0/101 (0%)		0/103 (0%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Pleural effusion	0/101 (0%)		2/103 (1.9%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Pulmonary embolism	3/101 (3%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Pulmonary haemorrhage	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Pneumothorax	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Skin and subcutaneous tissue disorders
Rash erythematous	0/101 (0%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Rash maculo-papular	0/101 (0%)		1/103 (1%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Surgical and medical procedures
Limb Operation	0/101 (0%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Vascular disorders
Deep vein thrombosis	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Embolism	0/101 (0%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		1/63 (1.6%)
Haemorrhage	1/101 (1%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		0/63 (0%)
Hypertension	4/101 (4%)		0/103 (0%)		2/100 (2%)		0/46 (0%)		0/63 (0%)
Hypertensive crisis	0/101 (0%)		0/103 (0%)		0/100 (0%)		1/46 (2.2%)		0/63 (0%)
Orthostatic hypotension	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		1/63 (1.6%)
Other (Not Including Serious) Adverse Events
	Atezolizumab and Bevacizumab		Atezolizumab		Sunitinib		Atezolizumab (Crossover)		Sunitinib (Crossover)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/101 (98%)		94/103 (91.3%)		99/100 (99%)		44/46 (95.7%)		57/63 (90.5%)
Blood and lymphatic system disorders
Anaemia	11/101 (10.9%)		19/103 (18.4%)		18/100 (18%)		2/46 (4.3%)		9/63 (14.3%)
Leukopenia	0/101 (0%)		0/103 (0%)		9/100 (9%)		0/46 (0%)		0/63 (0%)
Neutropenia	2/101 (2%)		1/103 (1%)		12/100 (12%)		0/46 (0%)		0/63 (0%)
Thrombocytopenia	6/101 (5.9%)		1/103 (1%)		15/100 (15%)		2/46 (4.3%)		4/63 (6.3%)
Endocrine disorders
Adrenal insufficiency	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		0/63 (0%)
Hypothyroidism	19/101 (18.8%)		12/103 (11.7%)		20/100 (20%)		8/46 (17.4%)		7/63 (11.1%)
Eye disorders
Dry eye	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		0/63 (0%)
Gastrointestinal disorders
Abdominal distension	8/101 (7.9%)		2/103 (1.9%)		3/100 (3%)		5/46 (10.9%)		7/63 (11.1%)
Abdominal pain	17/101 (16.8%)		8/103 (7.8%)		16/100 (16%)		10/46 (21.7%)		15/63 (23.8%)
Abdominal pain upper	4/101 (4%)		2/103 (1.9%)		9/100 (9%)		0/46 (0%)		0/63 (0%)
Constipation	30/101 (29.7%)		16/103 (15.5%)		30/100 (30%)		9/46 (19.6%)		14/63 (22.2%)
Diarrhoea	36/101 (35.6%)		20/103 (19.4%)		62/100 (62%)		13/46 (28.3%)		19/63 (30.2%)
Dry mouth	12/101 (11.9%)		12/103 (11.7%)		9/100 (9%)		5/46 (10.9%)		5/63 (7.9%)
Dyspepsia	8/101 (7.9%)		4/103 (3.9%)		20/100 (20%)		3/46 (6.5%)		4/63 (6.3%)
Gastrooesophageal reflux disease	7/101 (6.9%)		3/103 (2.9%)		13/100 (13%)		0/46 (0%)		0/63 (0%)
Gingival bleeding	7/101 (6.9%)		0/103 (0%)		1/100 (1%)		3/46 (6.5%)		2/63 (3.2%)
Nausea	40/101 (39.6%)		19/103 (18.4%)		46/100 (46%)		14/46 (30.4%)		21/63 (33.3%)
Oral pain	4/101 (4%)		0/103 (0%)		7/100 (7%)		0/46 (0%)		0/63 (0%)
Stomatitis	15/101 (14.9%)		3/103 (2.9%)		25/100 (25%)		6/46 (13%)		5/63 (7.9%)
Vomiting	20/101 (19.8%)		8/103 (7.8%)		21/100 (21%)		6/46 (13%)		16/63 (25.4%)
Haemorrhoids	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		2/63 (3.2%)
General disorders
Asthenia	7/101 (6.9%)		8/103 (7.8%)		7/100 (7%)		1/46 (2.2%)		7/63 (11.1%)
Chest pain	7/101 (6.9%)		5/103 (4.9%)		6/100 (6%)		4/46 (8.7%)		1/63 (1.6%)
Chills	5/101 (5%)		8/103 (7.8%)		13/100 (13%)		0/46 (0%)		0/63 (0%)
Fatigue	62/101 (61.4%)		52/103 (50.5%)		70/100 (70%)		19/46 (41.3%)		27/63 (42.9%)
Influenza like illness	8/101 (7.9%)		6/103 (5.8%)		3/100 (3%)		0/46 (0%)		0/63 (0%)
Mucosal inflammation	18/101 (17.8%)		4/103 (3.9%)		33/100 (33%)		6/46 (13%)		4/63 (6.3%)
Oedema peripheral	20/101 (19.8%)		12/103 (11.7%)		10/100 (10%)		8/46 (17.4%)		10/63 (15.9%)
Pain	16/101 (15.8%)		7/103 (6.8%)		10/100 (10%)		0/46 (0%)		0/63 (0%)
Pyrexia	19/101 (18.8%)		23/103 (22.3%)		10/100 (10%)		6/46 (13%)		10/63 (15.9%)
Infections and infestations
Nasopharyngitis	11/101 (10.9%)		8/103 (7.8%)		2/100 (2%)		0/46 (0%)		0/63 (0%)
Rhinitis	8/101 (7.9%)		6/103 (5.8%)		1/100 (1%)		0/46 (0%)		0/63 (0%)
Sinusitis	15/101 (14.9%)		5/103 (4.9%)		3/100 (3%)		4/46 (8.7%)		4/63 (6.3%)
Upper respiratory tract infection	14/101 (13.9%)		11/103 (10.7%)		5/100 (5%)		8/46 (17.4%)		2/63 (3.2%)
Urinary tract infection	10/101 (9.9%)		8/103 (7.8%)		3/100 (3%)		1/46 (2.2%)		4/63 (6.3%)
Pneumonia	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		1/63 (1.6%)
Injury, poisoning and procedural complications
Contusion	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		2/63 (3.2%)
Investigations
Alanine aminotransferase increased	14/101 (13.9%)		7/103 (6.8%)		15/100 (15%)		0/46 (0%)		0/63 (0%)
Aspartate aminotransferase increased	10/101 (9.9%)		7/103 (6.8%)		17/100 (17%)		0/46 (0%)		0/63 (0%)
Blood alkaline phosphatase increased	8/101 (7.9%)		3/103 (2.9%)		6/100 (6%)		0/46 (0%)		0/63 (0%)
Blood creatinine increased	13/101 (12.9%)		17/103 (16.5%)		14/100 (14%)		10/46 (21.7%)		8/63 (12.7%)
Platelet count decreased	2/101 (2%)		2/103 (1.9%)		6/100 (6%)		3/46 (6.5%)		0/63 (0%)
Weight decreased	18/101 (17.8%)		5/103 (4.9%)		10/100 (10%)		2/46 (4.3%)		6/63 (9.5%)
Blood lactate dehydrogenase increased	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		3/63 (4.8%)
Protein total increased	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		1/63 (1.6%)
Metabolism and nutrition disorders
Decreased appetite	23/101 (22.8%)		11/103 (10.7%)		30/100 (30%)		4/46 (8.7%)		15/63 (23.8%)
Dehydration	11/101 (10.9%)		5/103 (4.9%)		4/100 (4%)		3/46 (6.5%)		6/63 (9.5%)
Hypercalcaemia	10/101 (9.9%)		4/103 (3.9%)		4/100 (4%)		0/46 (0%)		0/63 (0%)
Hyperglycaemia	8/101 (7.9%)		13/103 (12.6%)		5/100 (5%)		5/46 (10.9%)		5/63 (7.9%)
Hyperkalaemia	15/101 (14.9%)		6/103 (5.8%)		6/100 (6%)		4/46 (8.7%)		4/63 (6.3%)
Hypoalbuminaemia	6/101 (5.9%)		2/103 (1.9%)		5/100 (5%)		3/46 (6.5%)		4/63 (6.3%)
Hypomagnesaemia	10/101 (9.9%)		2/103 (1.9%)		6/100 (6%)		2/46 (4.3%)		4/63 (6.3%)
Hyponatraemia	12/101 (11.9%)		5/103 (4.9%)		7/100 (7%)		5/46 (10.9%)		10/63 (15.9%)
Hypophosphataemia	6/101 (5.9%)		11/103 (10.7%)		11/100 (11%)		4/46 (8.7%)		4/63 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	40/101 (39.6%)		19/103 (18.4%)		19/100 (19%)		17/46 (37%)		15/63 (23.8%)
Back pain	19/101 (18.8%)		18/103 (17.5%)		20/100 (20%)		8/46 (17.4%)		11/63 (17.5%)
Muscle spasms	8/101 (7.9%)		2/103 (1.9%)		6/100 (6%)		4/46 (8.7%)		1/63 (1.6%)
Musculoskeletal pain	22/101 (21.8%)		10/103 (9.7%)		6/100 (6%)		9/46 (19.6%)		5/63 (7.9%)
Myalgia	12/101 (11.9%)		10/103 (9.7%)		15/100 (15%)		3/46 (6.5%)		7/63 (11.1%)
Neck pain	10/101 (9.9%)		5/103 (4.9%)		8/100 (8%)		3/46 (6.5%)		1/63 (1.6%)
Pain in extremity	17/101 (16.8%)		8/103 (7.8%)		17/100 (17%)		9/46 (19.6%)		6/63 (9.5%)
Flank pain	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		2/63 (3.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		0/63 (0%)
Nervous system disorders
Dizziness	13/101 (12.9%)		9/103 (8.7%)		13/100 (13%)		4/46 (8.7%)		6/63 (9.5%)
Dysgeusia	12/101 (11.9%)		3/103 (2.9%)		30/100 (30%)		0/46 (0%)		0/63 (0%)
Headache	35/101 (34.7%)		16/103 (15.5%)		23/100 (23%)		7/46 (15.2%)		13/63 (20.6%)
Neuropathy peripheral	5/101 (5%)		1/103 (1%)		5/100 (5%)		0/46 (0%)		0/63 (0%)
Paraesthesia	8/101 (7.9%)		8/103 (7.8%)		11/100 (11%)		1/46 (2.2%)		4/63 (6.3%)
Psychiatric disorders
Depression	9/101 (8.9%)		5/103 (4.9%)		7/100 (7%)		2/46 (4.3%)		4/63 (6.3%)
Insomnia	10/101 (9.9%)		7/103 (6.8%)		12/100 (12%)		3/46 (6.5%)		8/63 (12.7%)
Anxiety	8/101 (7.9%)		6/103 (5.8%)		6/100 (6%)		1/46 (2.2%)		6/63 (9.5%)
Renal and urinary disorders
Dysuria	1/101 (1%)		7/103 (6.8%)		2/100 (2%)		0/46 (0%)		0/63 (0%)
Haematuria	3/101 (3%)		10/103 (9.7%)		9/100 (9%)		4/46 (8.7%)		4/63 (6.3%)
Proteinuria	38/101 (37.6%)		10/103 (9.7%)		9/100 (9%)		21/46 (45.7%)		25/63 (39.7%)
Acute kidney injury	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		2/63 (3.2%)
Nocturia	6/101 (5.9%)		2/103 (1.9%)		4/100 (4%)		3/46 (6.5%)		1/63 (1.6%)
Respiratory, thoracic and mediastinal disorders
Cough	24/101 (23.8%)		26/103 (25.2%)		25/100 (25%)		14/46 (30.4%)		12/63 (19%)
Dysphonia	18/101 (17.8%)		2/103 (1.9%)		4/100 (4%)		9/46 (19.6%)		8/63 (12.7%)
Dyspnoea	19/101 (18.8%)		18/103 (17.5%)		18/100 (18%)		8/46 (17.4%)		10/63 (15.9%)
Dyspnoea exertional	5/101 (5%)		7/103 (6.8%)		8/100 (8%)		3/46 (6.5%)		2/63 (3.2%)
Epistaxis	29/101 (28.7%)		2/103 (1.9%)		12/100 (12%)		13/46 (28.3%)		5/63 (7.9%)
Nasal congestion	12/101 (11.9%)		11/103 (10.7%)		3/100 (3%)		5/46 (10.9%)		4/63 (6.3%)
Oropharyngeal pain	12/101 (11.9%)		11/103 (10.7%)		3/100 (3%)		6/46 (13%)		0/63 (0%)
Productive cough	0/101 (0%)		0/103 (0%)		0/100 (0%)		5/46 (10.9%)		2/63 (3.2%)
Rhinorrhoea	6/101 (5.9%)		6/103 (5.8%)		3/100 (3%)		3/46 (6.5%)		1/63 (1.6%)
Sinus congestion	7/101 (6.9%)		2/103 (1.9%)		2/100 (2%)		0/46 (0%)		0/63 (0%)
Skin and subcutaneous tissue disorders
Dry skin	13/101 (12.9%)		15/103 (14.6%)		10/100 (10%)		5/46 (10.9%)		2/63 (3.2%)
Night sweats	8/101 (7.9%)		5/103 (4.9%)		7/100 (7%)		4/46 (8.7%)		3/63 (4.8%)
Palmar-plantar erythrodysaesthesia syndrome	3/101 (3%)		0/103 (0%)		41/100 (41%)		0/46 (0%)		0/63 (0%)
Pruritus	27/101 (26.7%)		18/103 (17.5%)		10/100 (10%)		8/46 (17.4%)		7/63 (11.1%)
Rash	28/101 (27.7%)		24/103 (23.3%)		14/100 (14%)		12/46 (26.1%)		7/63 (11.1%)
Ecchymosis	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		0/63 (0%)
Hyperhidrosis	0/101 (0%)		0/103 (0%)		0/100 (0%)		0/46 (0%)		4/63 (6.3%)
Rash erythematous	0/101 (0%)		0/103 (0%)		0/100 (0%)		3/46 (6.5%)		1/63 (1.6%)
Vascular disorders
Hypertension	38/101 (37.6%)		10/103 (9.7%)		34/100 (34%)		12/46 (26.1%)		13/63 (20.6%)

Limitations/Caveats

[Not Specified]

More Information

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.