IMpower150: A Study of Atezolizumab in Combination With Carboplatin Plus (+) Paclitaxel With or Without Bevacizumab Compared With Carboplatin+Paclitaxel+Bevacizumab in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT02366143

Collaborator

(none)

1,202

Enrollment

240

Locations

Arms

68.3

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized, open-label study evaluated the safety and efficacy of atezolizumab (an engineered anti-programmed death-ligand 1 [PD-L1] antibody) in combination with carboplatin+paclitaxel with or without bevacizumab compared with treatment with carboplatin+paclitaxel+bevacizumab in chemotherapy-naïve participants with Stage IV non-squamous NSCLC. Participants were randomized in a 1:1:1 ratio to Arm A (Atezolizumab+Carboplatin+Paclitaxel), Arm B (Atezolizumab+Carboplatin+Paclitaxel+Bevacizumab), or Arm C (Carboplatin+Paclitaxel+Bevacizumab).

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody Drug: Bevacizumab Drug: Carboplatin Drug: Paclitaxel	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1202 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel With or Without Bevacizumab Compared With Carboplatin + Paclitaxel + Bevacizumab in Chemotherapy-Naïve Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer

Actual Study Start Date :

Mar 31, 2015

Actual Primary Completion Date :

Sep 13, 2019

Actual Study Completion Date :

Dec 7, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (Atezolizumab+Paclitaxel+Carboplatin) Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody Atezolizumab was administered as IV infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until loss of clinical benefit. Other Names: MPDL3280A RO5541267 Tecentriq Drug: Carboplatin Carboplatin was administered at area under the concentration-time curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first. Drug: Paclitaxel Paclitaxel was administered as IV infusion at a dose of 200 milligrams per square meter (mg/m^2) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.
Experimental: Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin) Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody Atezolizumab was administered as IV infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until loss of clinical benefit. Other Names: MPDL3280A RO5541267 Tecentriq Drug: Bevacizumab Bevacizumab was administered as IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, or death. Drug: Carboplatin Carboplatin was administered at area under the concentration-time curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first. Drug: Paclitaxel Paclitaxel was administered as IV infusion at a dose of 200 milligrams per square meter (mg/m^2) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.
Active Comparator: Arm C (Bevacizumab+Paclitaxel+Carboplatin) Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.	Drug: Bevacizumab Bevacizumab was administered as IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, or death. Drug: Carboplatin Carboplatin was administered at area under the concentration-time curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first. Drug: Paclitaxel Paclitaxel was administered as IV infusion at a dose of 200 milligrams per square meter (mg/m^2) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.

Arm

Intervention/Treatment

Experimental: Arm A (Atezolizumab+Paclitaxel+Carboplatin)

Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.

Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

Atezolizumab was administered as IV infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until loss of clinical benefit.

Other Names:

MPDL3280A

RO5541267

Tecentriq

Drug: Carboplatin

Carboplatin was administered at area under the concentration-time curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.

Drug: Paclitaxel

Paclitaxel was administered as IV infusion at a dose of 200 milligrams per square meter (mg/m^2) on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first.

Experimental: Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)

Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

Atezolizumab was administered as IV infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until loss of clinical benefit.

Other Names:

MPDL3280A

RO5541267

Tecentriq

Drug: Bevacizumab

Bevacizumab was administered as IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, or death.

Drug: Carboplatin

Drug: Paclitaxel

Active Comparator: Arm C (Bevacizumab+Paclitaxel+Carboplatin)

Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.

Drug: Bevacizumab

Bevacizumab was administered as IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, or death.

Drug: Carboplatin

Drug: Paclitaxel

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS), as Determined by the Investigator in Arm B Versus Arm C in the Teff-high WT Population and ITT-WT Population [Baseline until disease progression or death, whichever occurs first until data cut-off on 15 September 2017 (up to approximately 29 months)]
Progression Free Survival (PFS), as Determined by the Investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.
Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population [Baseline until death until data cut-off on 22 January 2018 (up to approximately 34 months)]
Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population [Baseline until death (up approximately 53 months)]
Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population

Secondary Outcome Measures

PFS, as Determined by the Independent Review Facility (IRF) in Arm B Versus Arm C in Teff-High-WT Population and ITT-WT Population [Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)]
PFS, as determined by the independent review facility (IRF) Using RECIST v1.1 in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.
PFS, as Determined by the Investigator in Arm B Versus Arm C in Teff High Population and ITT Population [Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)]
PFS, as determined by the investigator according to RECIST v1.1, in Arm B versus C in the Teff high population and ITT population.
PFS, as Determined by the Investigator in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population [Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)]
PFS, as determined by the investigator according to RECIST v1.1, in Arm A versus B in the Teff high-WT population and ITT-WT population.
PFS, as Determined by the Investigator in Arm B Versus Arm C by PD-L1 Subgroup [Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)]
PFS as Determined by the Investigator according to RECIST v1.1, in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
OS in Arm B Versus Arm C by PD-L1 Subgroup [Baseline until death (up to approximately 34 months)]
OS in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
OS in Arm A Versus Arm C by PD-L1 Subgroup [Baseline until death (up approximately 53 months)]
OS in Arm A Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
OS in Arm B Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population [Baseline until death (up to approximately 34 months)]
OS in Arm A Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population [Baseline until death (up approximately 53 months)]
OS in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population [Baseline until death (up approximately 53 months)]
Duration of Response (DOR), as Determined By Investigator in Arm B Versus Arm C [Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)]
DOR, as determined by investigator according to RECIST v1.1 in Arm B versus Arm C in the Teff high-WT population and the ITT-WT population.
Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator in the Teff-High-WT Population and ITT-WT Population [Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)]
Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator using RECIST v1.1 in the Teff-High-WT population and ITT-WT population.
OS Rates at Years 1 and 2 in Arm B Versus Arm C [Baseline to 2 years or death, whichever occurs first.]
OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.
OS Rates at Years 1 and 2 in Arm A Versus Arm C [Baseline to 2 years or death, whichever occurs first.]
OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.
Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms Determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score [Baseline up to approximately 29 months]
EORTC QLQ-C30 is a validated & reliable self-report measure (Aaronson et al.1993;Fitzsimmons et al.1999) that consists of 30 questions that assess 5 aspects of patient functioning (physical,emotional,role, cognitive,and social), 3 symptom scales (fatigue,nausea & vomiting, pain),global health/quality of life,and six single items (dyspnea,insomnia, appetite loss,constipation,diarrhea, and financial difficulties). EORTC QLQ-C30 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life);however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al.1998).
TTD in Patient-Reported Lung Cancer Symptoms as Determined by EORTC Quality-of-Life Questionnaire-Core Lung Cancer Module 13 (QLQ-LC13) Score [Baseline up to approximately 29 months]
QLQ-LC13 Quality-of-Life Questionnaire Lung Cancer Module incorporates one multiple-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998).
Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale [Baseline up to approximately 29 months]
The SILC (Symptoms in Lung Cancer) scale was used to assess patient-reported severity of lung cancer symptoms (chest pain, dyspnea, and cough). The SILC scale is a 9-item content validated self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a symptom severity score. The SILC questionnaire comprises three individual symptoms (dyspnea, cough, chest pain) and are scored at the individual symptom level, thus have a dyspnea score, chest pain score, and cough score. Each individual symptom score is calculated as the average of responses for the symptom items [e.g. Chest Pain Score=mean (item 1; item 2)]. An increase in score is suggestive of a worsening in symptomology (i.e. frequency or severity). A score change of ≥0.3 points for the dyspnea and cough symptom scores is considered to be clinically significant; whereas a score change of ≥0.5 points for the chest pain score is considered to be clinically significant.
Percentage of Participants With Adverse Events [Baseline up to data cutoff date 7 December 2020 (up to approximately 68 months)]
Percentage of participants with at least one adverse event.
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab [Baseline up to approximately 29 months]
Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Arm A and Arm B [Day 1 of Cycle 1 and 3 (Cycle length=21 days)]
The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes.
Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Arm A and Arm B [Day 21 of Cycles 1, 2 3, and 7 (Cycle length=21 days)]
Plasma Concentrations for Carboplatin in Arm A, Arm B, and Arm C [Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 h after carboplatin infusion (infusion duration=15 to 30 minutes) on D1 of Cy1,3 (Cycle length=21 days)]
Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C [Predose (same day of treatment administration), 5-10 minutes before end of paclitaxel infusion, 1 h after paclitaxel infusion (infusion duration=3 h) on D1 of Cy1,3 (Cycle length=21 days)]
Cmax of Bevacizumab in Arm B and Arm C [Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length=21 days)]
Cmin of Bevacizumab in Arm B and Arm C [Cycle 1 Day 1 and Cycle 2 Day 21 (Cycle length=21 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eastern Cooperative Oncology Group performance status 0 or 1
Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
Participants with no prior treatment for Stage IV non-squamous NSCLC
Known PD-L1 status as determined by immunohistochemistry assay performed on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening
Measurable disease as defined by RECIST v1.1
Adequate hematologic and end organ function

Exclusion Criteria:

Cancer-Specific Exclusions:

Active or untreated central nervous system metastases
Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome

General Medical Exclusions:

Pregnant or lactating women
History of autoimmune disease
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
Positive test for human immunodeficiency virus
Active hepatitis B or hepatitis C
Severe infection within 4 weeks prior to randomization
Significant cardiovascular disease
Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures

Exclusion Criteria Related to Medications:

Prior treatment with cluster of differentiation 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1, and anti-PD-L1 therapeutic antibodies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ironwood Cancer & Research Centers	Chandler	Arizona	United States	85224
2	Arizona Oncology Associates	Flagstaff	Arizona	United States	86001
3	Southern CA Permanente Med Grp	Bellflower	California	United States
4	Marin Cancer Care Inc	Greenbrae	California	United States	94904
5	Scripps Health	La Jolla	California	United States	92037
6	Chao Family Comprehensive Cancer Center UCI	Orange	California	United States	92868
7	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
8	Kaiser Permanente	Lonetree	Colorado	United States	80124
9	Danbury Hospital	Danbury	Connecticut	United States	06810
10	Yale Cancer Center	New Haven	Connecticut	United States	06520
11	Holy Cross Hospital Inc	Fort Lauderdale	Florida	United States	33308
12	Cancer Specialists of North Florida - Baptist South	Jacksonville	Florida	United States	32258
13	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
14	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida	United States	34952
15	Piedmont Cancer Institute, PC	Atlanta	Georgia	United States	30318
16	Rush University Medical Center	Chicago	Illinois	United States	60612
17	Univ of Chicago	Chicago	Illinois	United States	60637
18	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
19	Oncology Specialists, S.C.	Park Ridge	Illinois	United States	60068
20	Hematology-Oncology; Associates of the Quad Cities	Bettendorf	Iowa	United States	52722
21	Norton Cancer Institute	Louisville	Kentucky	United States	40202
22	New England Cancer Specialists	Scarborough	Maine	United States	04074
23	Mercy Medical Center	Baltimore	Maryland	United States	21202
24	Regional Cancer Care Associates	Bethesda	Maryland	United States	20817
25	Maryland Oncology Hematology, P.A.	Columbia	Maryland	United States	21044
26	St. Joseph Mercy Health System	Ann Arbor	Michigan	United States	48106
27	St. Luke's Regional Cancer Center	Duluth	Minnesota	United States	55805
28	Park Nicolett - Frauenshuh Cancer Center	Saint Louis Park	Minnesota	United States	55426
29	St. Luke's Cancer Institute	Kansas City	Missouri	United States	64111
30	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
31	Billings Clinic	Billings	Montana	United States	59102
32	Montana Cancer Specialists	Missoula	Montana	United States	59802
33	Comprehensive Cancer Centers of Nevada	Henderson	Nevada	United States	89014
34	Summit Medical Group	Berkeley Heights	New Jersey	United States	07922
35	Valley Hospital; Oncology Research	Paramus	New Jersey	United States	07652
36	Regional Cancer Care Associates LLC	Sewell	New Jersey	United States	08080
37	Montefiore Medical Center	Bronx	New York	United States	10467
38	Maimonides Medical Center	Brooklyn	New York	United States	11219
39	First Health of the Carolinas	Pinehurst	North Carolina	United States	28374
40	University of Cincinnati	Cincinnati	Ohio	United States	45203-0542
41	Mercy St Anne Hospital	Toledo	Ohio	United States	43623
42	Bend Memorial Clinic	Bend	Oregon	United States	97701
43	St. Charles Medical Center Bend; Cancer Care Of The Cascades	Bend	Oregon	United States	97701
44	Willamette Valley Cancer Insitute and Research Center	Springfield	Oregon	United States	97477
45	St. Luke's Cancer Care Associates	Bethlehem	Pennsylvania	United States	18015
46	Allegheny Cancer Center	Pittsburgh	Pennsylvania	United States	15212
47	Univ of Pittsburgh Medical Ctr	Pittsburgh	Pennsylvania	United States	15232
48	West Clinic	Germantown	Tennessee	United States	38138
49	Tennessee Cancer Specialists	Knoxville	Tennessee	United States	37920
50	Houston Methodist Cancer Center	Houston	Texas	United States	77030
51	Longview Cancer Center	Longview	Texas	United States	75601
52	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
53	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
54	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
55	Virginia Cancer Institute	Richmond	Virginia	United States	23226
56	Blue Ridge Cancer Care	Roanoke	Virginia	United States	24014
57	MultiCare Regional Cancer Center - Auburn	Auburn	Washington	United States	98002-4117
58	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
59	Virginia Mason Medical Center	Seattle	Washington	United States	98101
60	Medical Oncology Associates	Spokane	Washington	United States	99208
61	West Virginia University; Mary Babb Randolph Can Ctr	Morgantown	West Virginia	United States	26506
62	Centro Medico Austral	Buenos Aires		Argentina	1019
63	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires		Argentina	C1125ABD
64	Sanatorio Allende	Cordoba		Argentina	X5000JHQ
65	Centro Oncologico Riojano Integral (CORI)	La Rioja		Argentina	F5300COE
66	Hospital Provincial del Centenario	Rosario		Argentina	2000
67	Fundacion Koriza	Santa Rosa		Argentina	6300
68	Centro de Investigacion; Clinica - Clinica Viedma S.A.	Viedma		Argentina	R8500ACE
69	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
70	Concord Repatriation General Hospital	Concord	New South Wales	Australia	2139
71	Nepean Cancer Care Centre	Sydney	New South Wales	Australia	2747
72	Prince Charles Hospital; Department of Medical Oncology	Chermside	Queensland	Australia	4032
73	Townsville Hospital	Townsville	Queensland	Australia	4810
74	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
75	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
76	Adelaide Cancer Centre	Kurralta Park	South Australia	Australia	5037
77	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
78	Launceston General Hospital	Launceston	Tasmania	Australia	7250
79	Frankston Hospital	Frankston	Victoria	Australia	3199
80	Austin Health	Heidelberg	Victoria	Australia	3084
81	Cabrini Hospital Malvern	Malvern	Victoria	Australia	3144
82	The Alfred Hospital	Prahan	Victoria	Australia	3181
83	Sunshine Hospital	St Albans	Victoria	Australia	3021
84	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
85	Paracelsus Medizinische Privatuniversität	Salzburg		Austria	5020
86	Klinikum Wels-Grieskirchen	Wels		Austria	4600
87	CHU de Liège	Liège		Belgium	4000
88	Clinique Ste-Elisabeth	Namur		Belgium	5000
89	CETUS Hospital Dia Oncologia	Uberaba	MG	Brazil	38082-049
90	Instituto Do Cancer Delondrina_X; Unidade De Pesquisa Clinica	Londrina	PR	Brazil	86 015 520
91	Liga Norte Riograndense Contra O Câncer	Natal	RN	Brazil	59040150
92	IPCEM; Instituto de Pesquisa de Estudos Multicêntricos	Caxias do Sul	RS	Brazil	95070-560
93	Hospital Mae de Deus	Porto Alegre	RS	Brazil	90470-340
94	Hospital de Cancer de Barretos	Barretos	SP	Brazil	14784-400
95	Instituto Ribeirãopretano de Combate Ao Câncer; Centro Especializado De Oncologia	Ribeirão Preto	SP	Brazil	14015-130
96	Hospital de Base de Sao Jose do Rio Preto	Sao Jose do Rio Preto	SP	Brazil	15090-000
97	Hospital A. C. Camargo; Oncologia	Sao Paulo	SP	Brazil	01509-010
98	Multiprofile Hospital for Active Treatment Central Onco Hospital OOD	Plovdiv		Bulgaria	4000
99	MHAT Serdika, EOOD	Sofia		Bulgaria	1303
100	Lakeridge Health Center	Oshawa	Ontario	Canada	L1J 2J2
101	Clinica Santa Maria	Santiago		Chile	0
102	Health & Care SPA	Santiago		Chile	7500006
103	Sociedad de Investigaciones Medicas Ltda (SIM)	Temuco		Chile	4810469
104	Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest	Bordeaux		France	33076
105	CHU de Grenoble	Grenoble		France	38043
106	Centre Jean Bernard Clinique Victor Hugo	Le Mans		France	72015
107	Hôpital Saint Joseph	Marseille		France	13008
108	Hopital Nord AP-HM	Marseille		France	13015
109	Hôpital Européen Georges Pompidou	Paris		France	75908
110	CHU de Bordeaux	Pessac		France	33600
111	Service de Pneumologie Centre Hospitalier Régional La Réunion Site Felix Guyon	Saint Denis Cedex		France	97405
112	CH de Saint Quentin	Saint Quentin		France	2100
113	Centre Hospitalier Intercommunal Toulon - La Seyne sur Mer	Toulon		France	83000
114	Hôpital d'Instruction des Armées de Sainte Anne; Service de Pneumologie	Toulon		France	83000
115	Hôpital Larrey;Université Paul Sabatier	Toulouse		France	31059
116	Zentralklinikum Augsburg	Augsburg		Germany	86156
117	Helios Klinikum Emil von Behring GmbH	Berlin		Germany	14165
118	Ev.Krankenhaus Bielefeld gGmbH; Klinik für Innere Medizin und Geriatrie	Bielefeld		Germany	33611
119	Augusta Kranken-Anstalt gGmbH	Bochum		Germany	44791
120	Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden	Dresden		Germany	01307
121	St. Elisabethen Krankenhaus	Frankfurt am Main		Germany	60487
122	LungenClinic Großhansdorf GmbH	Großhansdorf		Germany	22927
123	Krankenhaus Martha-Maria; Halle-Dolau gGmbH	Halle		Germany	06120
124	Asklepios Klinik Harburg	Hamburg		Germany	21075
125	Lungenklinik Hemer	Hemer		Germany	58675
126	Universität Des Saarlandes; Klinik für Innere Medizin V	Homburg		Germany	66421
127	Kliniken der Stadt Koln gGmbH; Lungenklinik Onkologische Ambulanz	Koln		Germany	51109
128	Klinik Loewenstein gGmbH; Onk & Pal	Loewenstein		Germany	74245
129	Klinikum Bogenhausen	München		Germany	81925
130	Krankenhaus Barmherzige Bruder Regensburg	Regensburg		Germany	93049
131	Klinikum der Universität Regensburg	Regensburg		Germany	93053
132	Stiftung Mathias-Spital Rheine	Rheine		Germany	48431
133	AORN A Cardarelli	Napoli	Campania	Italy	80131
134	Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica	Roma	Lazio	Italy	00128
135	Azienda Ospedaliera San Camillo Forlanini	Roma	Lazio	Italy	00152
136	Università Cattolica Del S Cuore	Roma	Lazio	Italy	00168
137	Istituto Nazionale per la Ricerca sul Cancro di Genova	Genova	Liguria	Italy	16132
138	ASL 3 Genovese; DSM	Genova	Liguria	Italy	16147
139	A.O.U. Maggiore della Carità	Novara	Piemonte	Italy	28100
140	Azienda Unita Sanitaria Locale N1 Sassari; Unita Operativa Di Oncologia Medica	Sassari	Sardegna	Italy	07100
141	Policlinico Vittorio Emanuele	Catania	Sicilia	Italy	95123
142	Ospedale Versilia	Lido Di Camaiore	Toscana	Italy	55043
143	Ospedale Civile - Livorno	Livorno	Toscana	Italy	57124
144	National Hospital Organization Shikoku Cancer Center	Ehime		Japan	791-0280
145	National Hospital Organization Kyushu Medical Center	Fukuoka		Japan	810-8563
146	NHO Kyushu Cancer Center	Fukuoka		Japan	811-1395
147	Kurume University Hospital	Fukuoka		Japan	830-0011
148	Kanagawa Cardiovascular and Respiratory Center	Kanagawa		Japan	236-0051
149	Kitasato University Hospital	Kanagawa		Japan	252-0375
150	Kyoto University Hospital	Kyoto		Japan	606-8507
151	Miyagi Cancer Center	Miyagi		Japan	981-1293
152	Niigata Cancer Center Hospital	Niigata		Japan	951-8566
153	Osaka City University Hospital	Osaka		Japan	545-8586
154	National Hospital Organization Osaka Toneyama Medical Center	Osaka		Japan	560-8552
155	Toranomon Hospital	Tokyo		Japan	105-8470
156	Center Hospital of the National Center for Global Health and Medicine	Tokyo		Japan	162-0052
157	Kyorin University Hospital	Tokyo		Japan	181-8611
158	Wakayama Medical University Hospital	Wakayama		Japan	641-8510
159	Riga East Clinical University Hospital Latvian Oncology Centre	Riga		Latvia	LV-1079
160	Pauls Stradins Clinical University Hospital	Rīga		Latvia	LV-1002
161	National Cancer Institute	Vilnius		Lithuania	08660
162	Centro Universitario Contra El Cancer	Monterrey		Mexico	64020
163	Cancerologia de Queretaro	Queretaro		Mexico	76090
164	Centro Hemato Oncologico Privado; Oncologia	Toluca		Mexico	50080
165	Jeroen Bosch Ziekenhuis	'S Hertogenbosch		Netherlands	5223 GZ
166	Amsterdam UMC Location VUMC	Amsterdam		Netherlands	1081 HV
167	Amphia Ziekenhuis; Afdeling Longziekten	Breda		Netherlands	4818 CK
168	Ziekenhuis Gelderse Vallei	EDE		Netherlands	6716 RP
169	Tergooiziekenhuizen	Hilversum		Netherlands	1201 DA
170	Spaarne Gasthuis; Spaarne Ziekenhuis	Hoofddorp		Netherlands	2134 TM
171	Maastricht University Medical Center	Maastricht		Netherlands	6229 HX
172	St. Antonius Ziekenhuis; R&D Long	Nieuwegein		Netherlands	3435 CM
173	Erasmus MC; Afdeling Longziekten	Rotterdam		Netherlands	3015 GD
174	Maasstad ziekenhuis	Rotterdam		Netherlands	3079 DZ
175	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands	3584 CX
176	Gelre Ziekenhuizen, Zutphen	Zutphen		Netherlands	7207 AE
177	Centro Medico Monte Carmelo	Arequipa		Peru	04001
178	Centro Especializado de Enfermedades Neoplásicas	Arequipa		Peru
179	Instituto Nacional de Enfermedades Neoplasicas	Lima		Peru	Lima 34
180	Centro Hospitalar E Universitário de Coimbra EPE	Coimbra		Portugal	3000-602
181	Instituto Portugues Oncologia de Lisboa Francisco Gentil EPE	Lisboa		Portugal	1099-023
182	Hospital Pulido Valente; Servico de Pneumologia	Lisboa		Portugal	1796-001
183	Centro Hospitalar do Porto - Hospital de Santo António	Porto		Portugal	4099-001
184	Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe	Porto		Portugal	4200-072
185	Hospital de Sao Joao; Servico de Pneumologia	Porto		Portugal	4200
186	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast	Russian Federation	143423
187	Russian Oncology Research Center n.a. N.N. Blokhin	Moscow		Russian Federation	115478
188	Clinical Oncology Dispensary	Omsk		Russian Federation	644013
189	Evromedservis LCC	Pushkin		Russian Federation	196603
190	City Clinical Oncology Dispensary	Saint-Petersburg		Russian Federation	197022
191	National Cancer Centre; Medical Oncology	Singapore		Singapore	169610
192	Univerzitna nemocnica Bratislava	Bratislava		Slovakia	813 69
193	Narodny onkologicky ustav	Bratislava		Slovakia	833 10
194	POKO Poprad s.r.o.	Poprad		Slovakia	058 01
195	Instituto Catalan de Oncologia de Hospitalet (ICO); Servicio de Farmacia	L'Hospitalet de Llobregat	Barcelona	Spain	08908
196	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona	Spain	8208
197	Hospital Universitario Marques de Valdecilla	Santander	Cantabria	Spain	39008
198	Hospital Universitario Son Espases	Palma De Mallorca	Islas Baleares	Spain	07014
199	Hospital Universitario Insular de Gran Canaria	Las Palmas de Gran Canaria	LAS Palmas	Spain	35016
200	Complejo Hospitalario U. de Ourense	Ourense	Orense	Spain	32005
201	Hospital Lluis Alcanyis De Xativa	Xativa	Valencia	Spain	46800
202	Hospital del Mar	Barcelona		Spain	08003
203	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona		Spain	08035
204	Hospital Clinic de Barcelona	Barcelona		Spain	08036
205	Hospital Universitario Reina Sofia	Cordoba		Spain	14004
206	Hospital Lucus Augusti; Servicio de Oncologia	Lugo		Spain	27003
207	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid		Spain	28007
208	Hospital Universitario La Paz	Madrid		Spain	280146
209	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid		Spain	28034
210	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid		Spain	28040
211	Hospital Universitario Fundación Jimenez Díaz	Madrid		Spain	28040
212	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
213	Hospital Universitario HM Sanchinarro-CIOCC	Madrid		Spain	28050
214	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
215	Kantonsspital Baselland	Bruderholz		Switzerland	4101
216	Luzerner Kantonsspital Sursee	Luzern		Switzerland	6000
217	Kantonsspital St. Gallen; Onkologie/Hämatologie	St. Gallen		Switzerland	9007
218	Changhua Christian Hospital; Hematology-Oncology	Changhua		Taiwan	500
219	Kaohsiung Medical University Hospital; Department of Urology	Kaohsiung City		Taiwan	807
220	Chi Mei Medical Center Liou Ying Campus	Liuying Township		Taiwan	736
221	Chang Gung Memorial Hospital Chiayi	Putzu		Taiwan	613
222	National Cheng Kung Univ Hosp	Tainan		Taiwan	00704
223	National Taiwan Uni Hospital	Taipei City		Taiwan	10041
224	Cheng Hsin General Hospital	Taipei		Taiwan	112
225	Tri-Service General Hospital	Taipei		Taiwan	11490
226	Chang Gung Medical Foundation Linkou Branch	Taoyuan City		Taiwan	333
227	Taichung Veterans General Hospital	Xitun Dist.		Taiwan	40705
228	ME Bukovinian Clinical Oncology Center	Chernivtsi	Chernihiv Governorate	Ukraine	58013
229	Municipal Institution City Clinical Hospital #4 of Dnipro City Council - PPDS; Dept of Chemotherapy	Dnipropetrovsk	Katerynoslav Governorate	Ukraine	49102
230	Uzhgorod Central City Clinical Hospital	Uzhhorod	Katerynoslav Governorate	Ukraine	88000
231	MNPE Zaporizhzhia Regional Antitumor Center ZRC	Zaporizhzhia	Katerynoslav Governorate	Ukraine	69040
232	Communal Non profit Enterprise Regional Center of Oncology; Oncosurgical dept of thoracic organs	Kharkiv	Kharkiv Governorate	Ukraine	61070
233	MNPE Transcarpathian Antitumor Center of the Transcarpathian Regional Council; Chemotherapy Dept	Uzhhorod	Kherson Governorate	Ukraine	88014
234	Municipal Institution SubCarpathian Clinical Oncological Centre; Surgical department#2	Ivano-Frankivsk	KIEV Governorate	Ukraine	76018
235	Communal Nonprofit Enterprise Podilsky Regional Center Of Oncology OfTheVinnytsia Regional Council	Vinnytsia	KIEV Governorate	Ukraine	21029
236	SI Institute of Medical Radiology n.a. S.P. Hryhoriev of NAMS of Ukraine	Kharkiv		Ukraine	61024
237	ME Kryviy Rih Oncology Dispensary of Dnipropetrovs'k Regional Council; Chemotherapy Department	Kryvyi Rih		Ukraine	50048
238	Kyiv City Clinical Oncological Center	Kyiv		Ukraine	03115
239	Poltava Regional Clinical Oncology Dispensary of Poltava Regional Council; Thoracic department	Poltava		Ukraine	36011
240	Regional Municipal Institution Sumy Regional Clinical Oncology Dispensary	Sumy		Ukraine	40005

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT02366143

Other Study ID Numbers:

GO29436
2014-003207-30

First Posted:

Feb 19, 2015

Last Update Posted:

Sep 23, 2021

Last Verified:

Aug 1, 2021

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung

Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	Arm C	Arm B	Arm A
Arm/Group Description	Bevacizumab+Paclitaxel+Carboplatin	Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin	Atezolizumab+Paclitaxel+Carboplatin
Period Title: Overall Study
STARTED	400	400	402
COMPLETED	0	0	0
NOT COMPLETED	400	400	402

Baseline Characteristics

Arm/Group Title	Arm C	Arm B	Arm A	Total
Arm/Group Description	Bevacizumab+Paclitaxel+Carboplatin	Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin	Atezolizumab+Paclitaxel+Carboplatin	Total of all reporting groups
Overall Participants	400	400	402	1202
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.1 (9.3)	63.0 (9.5)	62.3 (9.2)	62.8 (9.3)
Sex: Female, Male (Count of Participants)
Female	161 40.3%	160 40%	161 40%	482 40.1%
Male	239 59.8%	240 60%	241 60%	720 59.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.3%	3 0.8%	0 0%	4 0.3%
Asian	46 11.5%	56 14%	48 11.9%	150 12.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	12 3%	3 0.8%	9 2.2%	24 2%
White	335 83.8%	322 80.5%	331 82.3%	988 82.2%
More than one race	0 0%	3 0.8%	4 1%	7 0.6%
Unknown or Not Reported	6 1.5%	13 3.3%	10 2.5%	29 2.4%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS), as Determined by the Investigator in Arm B Versus Arm C in the Teff-high WT Population and ITT-WT Population
Description	Progression Free Survival (PFS), as Determined by the Investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.
Time Frame	Baseline until disease progression or death, whichever occurs first until data cut-off on 15 September 2017 (up to approximately 29 months)

Outcome Measure Data

Analysis Population Description
Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	356	336
Teff-high WT Population	11.3	6.8
ITT-WT Population	8.3	6.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	ITT-WT population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95% 0.52 to 0.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Teff-high WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95% 0.38 to 0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
Description	Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
Time Frame	Baseline until death until data cut-off on 22 January 2018 (up to approximately 34 months)

Outcome Measure Data

Analysis Population Description
ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	359	337
Median (95% Confidence Interval) [Months]	19.2	14.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0164
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95% 0.64 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population
Description	Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population
Time Frame	Baseline until death (up approximately 53 months)

Outcome Measure Data

Analysis Population Description
ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	350	338
Median (95% Confidence Interval) [Months]	19.0	14.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0528
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.842
	Confidence Interval	(2-Sided) 95% 0.707 to 1.002
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	PFS, as Determined by the Independent Review Facility (IRF) in Arm B Versus Arm C in Teff-High-WT Population and ITT-WT Population
Description	PFS, as determined by the independent review facility (IRF) Using RECIST v1.1 in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.
Time Frame	Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Outcome Measure Data

Analysis Population Description
Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	356	336
Teff-high WT Population	10.7	7.0
ITT-WT Population	8.5	7.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	ITT-WT population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95% 0.59 to 0.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Teff-high WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.564
	Confidence Interval	(2-Sided) 95% 0.418 to 0.760
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	PFS, as Determined by the Investigator in Arm B Versus Arm C in Teff High Population and ITT Population
Description	PFS, as determined by the investigator according to RECIST v1.1, in Arm B versus C in the Teff high population and ITT population.
Time Frame	Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Outcome Measure Data

Analysis Population Description
Teff-high population is defined as the patients in the ITT population with Teff signature expression >=-1.91. ITT population is defined as all randomized patients, regardless of receipt of the assigned treatment.

Arm/Group Title	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	400	400
Teff-high Population	11.3	6.8
ITT Population	8.3	6.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Teff-high Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.492
	Confidence Interval	(2-Sided) 95% 0.374 to 0.649
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	ITT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.610
	Confidence Interval	(2-Sided) 95% 0.517 to 0.720
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	PFS, as Determined by the Investigator in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population
Description	PFS, as determined by the investigator according to RECIST v1.1, in Arm A versus B in the Teff high-WT population and ITT-WT population.
Time Frame	Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Outcome Measure Data

Analysis Population Description
Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
Measure Participants	348	356
Teff-high WT	6.3	11.3
ITT-WT	6.3	8.3

7. Secondary Outcome

Title	PFS, as Determined by the Investigator in Arm B Versus Arm C by PD-L1 Subgroup
Description	PFS as Determined by the Investigator according to RECIST v1.1, in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
Time Frame	Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Outcome Measure Data

Analysis Population Description
The PD-L1-selected WT populations are defined as the PD-L1-selected populations (TC2/3 or IC2/3 population or TC1/2/3 or IC1/2/3 population) excluding patients with a sensitizing EGFR mutation or ALK translocation.

Arm/Group Title	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	190	164
TC2/3 or IC2/3 Subgroup	11.1	6.8
TC1/2/3 or IC1/2/3 Subgroup	11.0	6.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	TC2/3 or IC2/3 Subgroup
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.471
	Confidence Interval	(2-Sided) 95% 0.352 to 0.647
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	TC1/2/3 or IC1/2/3 Subgroup
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.486
	Confidence Interval	(2-Sided) 95% 0.386 to 0.639
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	OS in Arm B Versus Arm C by PD-L1 Subgroup
Description	OS in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
Time Frame	Baseline until death (up to approximately 34 months)

Outcome Measure Data

Analysis Population Description
The PD-L1-selected WT populations are defined as the PD-L1-selected populations (TC2/3 or IC2/3 population or TC1/2/3 or IC1/2/3 population) excluding patients with a sensitizing EGFR mutation or ALK translocation.

Arm/Group Title	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	192	165
TC 2/3 or IC2/3 Population	22.2	16.7
TC1/2/3 or IC1/2/3 Population	22.5	16.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	TC2/3 or IC2/3, WT ITT
	Type of Statistical Test	Superiority
	Comments	Unstratified Analysis

Statistical Test of Hypothesis	p-Value	0.2765
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.824
	Confidence Interval	(2-Sided) 95% 0.580 to 1.169
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	TC1/2/3 or IC1/2/3, WT ITT
	Type of Statistical Test	Superiority
	Comments	Unstratified Analysis

Statistical Test of Hypothesis	p-Value	0.0829
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.771
	Confidence Interval	(2-Sided) 95% 0.575 to 1.035
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	OS in Arm A Versus Arm C by PD-L1 Subgroup
Description	OS in Arm A Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
Time Frame	Baseline until death (up approximately 53 months)

Outcome Measure Data

Analysis Population Description
PD-L1 WT populations are defined as the PD-L1 populations (TC2/3 or IC2/3 population or TC1/2/3 or IC1/2/3 population) excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	185	165
TC2/3 or IC2/3 Population	26.1	17.0
TC1/2/3 or IC1/2/3 Population	24.4	16.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	TC1/2/3 or IC1/2/3 ITT-WT
	Type of Statistical Test	Superiority
	Comments	Unstratified Analysis

Statistical Test of Hypothesis	p-Value	0.0073
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.709
	Confidence Interval	(2-Sided) 95% 0.551 to 0.913
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	TC2/3 or IC2/3 Population
	Type of Statistical Test	Superiority
	Comments	Unstratified Analysis

Statistical Test of Hypothesis	p-Value	0.0097
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.662
	Confidence Interval	(2-Sided) 95% 0.484 to 0.907
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	OS in Arm B Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population
Description
Time Frame	Baseline until death (up to approximately 34 months)

Outcome Measure Data

Analysis Population Description
Teff-high WT population, defined as the Teff-high population excluding patients with activating EGFR mutation or ALK translocation. Teff-high population, defined as participants in the ITT population with Teff signature expression >=-1.91. ITT population, defined as all randomized patients, regardless of receipt of the assigned treatment.

Arm/Group Title	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	400	400
Teff High-WT Population	25.0	16.7
Teff High Population	25.2	16.7
ITT Population	19.8	14.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Teff high-WT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.2843
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.831
	Confidence Interval	(2-Sided) 95% 0.592 to 1.167
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Teff high
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.1861
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.802
	Confidence Interval	(2-Sided) 95% 0.579 to 1.113
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	ITT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0060
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.764
	Confidence Interval	(2-Sided) 95% 0.630 to 0.926
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	OS in Arm A Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population
Description
Time Frame	Baseline until death (up approximately 53 months)

Outcome Measure Data

Analysis Population Description
Teff-high WT population, defined as Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. Teff-high population, defined as patients in the ITT population with Teff signature expression >=-1.91. ITT population is defined as all randomized patients, regardless of receipt of the assigned treatment.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	402	400
Teff-high WT Population	21.3	16.3
Teff-high Population	21.0	16.7
ITT Population	19.0	15.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Teff high-WT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0894
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.786
	Confidence Interval	(2-Sided) 95% 0.595 to 1.038
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Teff high
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.1276
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.815
	Confidence Interval	(2-Sided) 95% 0.626 to 1.061
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	ITT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0681
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.861
	Confidence Interval	(2-Sided) 95% 0.733 to 1.011
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	OS in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population
Description
Time Frame	Baseline until death (up approximately 53 months)

Outcome Measure Data

Analysis Population Description
Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
Measure Participants	350	359
Teff High-WT Population	21.3	25.8
ITT-WT Population	19.0	19.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Teff high-WT ITT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.4599
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.901
	Confidence Interval	(2-Sided) 95% 0.683 to 1.188
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Duration of Response (DOR), as Determined By Investigator in Arm B Versus Arm C
Description	DOR, as determined by investigator according to RECIST v1.1 in Arm B versus Arm C in the Teff high-WT population and the ITT-WT population.
Time Frame	Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Outcome Measure Data

Analysis Population Description
Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	224	159
Teff high-WT Population	11.2	5.7
ITT-WT Population	9.0	5.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	ITT-WT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.523
	Confidence Interval	(2-Sided) 95% 0.406 to 0.675
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Teff-high WT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.420
	Confidence Interval	(2-Sided) 95% 0.283 to 0.624
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator in the Teff-High-WT Population and ITT-WT Population
Description	Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator using RECIST v1.1 in the Teff-High-WT population and ITT-WT population.
Time Frame	Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

Outcome Measure Data

Analysis Population Description
Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	347	353	331
Teff-high WT Population	54.0	69.3	53.5
ITT-WT Population	49.3	63.5	48.0

15. Secondary Outcome

Title	OS Rates at Years 1 and 2 in Arm B Versus Arm C
Description	OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.
Time Frame	Baseline to 2 years or death, whichever occurs first.

Outcome Measure Data

Analysis Population Description
Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	235	196
1-Year Teff-high WT Population	68.63	58.74
1-Year ITT-WT Population	67.32	60.63
2-Year Teff-high WT Population	52.03	41.70
2-Year ITT-WT Population	43.42	33.71

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	1-Year ITT-WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0697
	Comments
	Method	Z-test
	Comments

Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	6.68
	Confidence Interval	(2-Sided) 95% -0.54 to 13.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	2-Year ITT-WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0347
	Comments
	Method	Z-test
	Comments

Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	9.71
	Confidence Interval	(2-Sided) 95% 0.70 to 18.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	1-Year Teff-high WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0890
	Comments
	Method	Z-test
	Comments

Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	9.89
	Confidence Interval	(2-Sided) 95% -1.51 to 21.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	2-Year Teff-high WT Population
	Type of Statistical Test	Other
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.1336
	Comments
	Method	Z-test
	Comments

Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	10.34
	Confidence Interval	(2-Sided) 95% -3.17 to 23.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	OS Rates at Years 1 and 2 in Arm A Versus Arm C
Description	OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.
Time Frame	Baseline to 2 years or death, whichever occurs first.

Outcome Measure Data

Analysis Population Description
Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	222	197
1-Year Teff-high WT Population	67.48	56.92
2-Year Teff-high WT Population	46.01	38.74
1-Year ITT-WT Population	64.06	59.89
2-Year ITT-WT Population	41.45	31.79

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	1-Year ITT-WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.2624
	Comments
	Method	Z-test
	Comments

Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	4.18
	Confidence Interval	(2-Sided) 95% -3.13 to 11.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	2-Year ITT-WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0088
	Comments
	Method	Z-test
	Comments

Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	9.67
	Confidence Interval	(2-Sided) 95% 2.43 to 16.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	1-Year Teff-high WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.0649
	Comments
	Method	Z-test
	Comments

Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	10.56
	Confidence Interval	(2-Sided) 95% -0.65 to 21.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	2-Year Teff-high WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.2120
	Comments
	Method	Z-test
	Comments

Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	7.27
	Confidence Interval	(2-Sided) 95% -4.15 to 18.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms Determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score
Description	EORTC QLQ-C30 is a validated & reliable self-report measure (Aaronson et al.1993;Fitzsimmons et al.1999) that consists of 30 questions that assess 5 aspects of patient functioning (physical,emotional,role, cognitive,and social), 3 symptom scales (fatigue,nausea & vomiting, pain),global health/quality of life,and six single items (dyspnea,insomnia, appetite loss,constipation,diarrhea, and financial difficulties). EORTC QLQ-C30 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life);however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al.1998).
Time Frame	Baseline up to approximately 29 months

Outcome Measure Data

Analysis Population Description
Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	348	356	336
Dyspnea in Teff-high WT Population	NA	NA	NA
Dyspnea in ITT-WT Population	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm C (Bevacizumab+Paclitaxel+Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Teff-high WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.6899
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.909
	Confidence Interval	(2-Sided) 95% 0.571 to 1.450
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Teff-high WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.1043
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.671
	Confidence Interval	(2-Sided) 95% 0.413 to 1.089
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm C (Bevacizumab+Paclitaxel+Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	ITT WT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.1730
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.232
	Confidence Interval	() 95% 0.912 to 1.665
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	ITT WT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.6145
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.084
	Confidence Interval	(2-Sided) 95% 0.792 to 1.483
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	TTD in Patient-Reported Lung Cancer Symptoms as Determined by EORTC Quality-of-Life Questionnaire-Core Lung Cancer Module 13 (QLQ-LC13) Score
Description	QLQ-LC13 Quality-of-Life Questionnaire Lung Cancer Module incorporates one multiple-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998).
Time Frame	Baseline up to approximately 29 months

Outcome Measure Data

Analysis Population Description
Teff-high WT population is defined as the Teff-high population excluding patients with an activating EGFR mutation or ALK translocation. ITT-WT population is defined as the ITT population excluding patients with an activating EGFR mutation or ALK translocation.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	348	356	336
Cough in Teff-high WT Population	NA	NA	NA
Dyspnea in Teff-high WT Population	NA	NA	NA
Chest Pain in Teff-high WT Population	NA	22.2	18.4
Arm and/or Shoulder Pain in Teff-high WT	NA	19.5	NA
Cough in ITT-WT Population	NA	NA	NA
Dyspnea in ITT-WT Population	21.9	NA	NA
Arm and/or Shoulder Pain in ITT-WT	NA	19.5	NA
Pain in Chest in ITT-WT Population	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm C (Bevacizumab+Paclitaxel+Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Cough for Teff-high WT ITT population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.8816
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.041
	Confidence Interval	(2-Sided) 95% 0.614 to 1.763
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Cough for Teff-high WT ITT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.2995
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.741
	Confidence Interval	(2-Sided) 95% 0.419 to 1.309
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm C (Bevacizumab+Paclitaxel+Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Dyspnea in Teff-high WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.7578
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.936
	Confidence Interval	(2-Sided) 95% 0.616 to 1.422
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Dyspnea in Teff-high WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.8470
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.041
	Confidence Interval	(2-Sided) 95% 0.694 to 1.560
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm C (Bevacizumab+Paclitaxel+Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Pain in Chest in Teff-high WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.1289
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.659
	Confidence Interval	(2-Sided) 95% 0.383 to 1.133
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Pain in Chest in Teff-high WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.2381
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.729
	Confidence Interval	(2-Sided) 95% 0.430 to 1.235
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Arm C (Bevacizumab+Paclitaxel+Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Arm and/or Shoulder Pain in Teff-high WT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.7163
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.090
	Confidence Interval	(2-Sided) 95% 0.685 to 1.732
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Arm and/or Shoulder Pain in Teff-high WT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.1502
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.693
	Confidence Interval	(2-Sided) 95% 0.420 to 1.145
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Arm C (Bevacizumab+Paclitaxel+Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Cough in ITT-WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.9568
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.010
	Confidence Interval	(2-Sided) 95% 0.713 to 1.430
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Cough in ITT-WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.5377
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.891
	Confidence Interval	(2-Sided) 95% 0.619 to 1.284
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Arm C (Bevacizumab+Paclitaxel+Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Dyspnea in ITT-WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.4012
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.893
	Confidence Interval	(2-Sided) 95% 0.685 to 1.163
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Dyspnea in ITT-WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.7149
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.050
	Confidence Interval	(2-Sided) 95% 0.809 to 1.363
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Arm C (Bevacizumab+Paclitaxel+Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Arm and/or Shoulder Pain in ITT-WT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.7126
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.057
	Confidence Interval	(2-Sided) 95% 0.786 to 1.422
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Arm and/or Shoulder Pain in ITT-WT
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.6053
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.921
	Confidence Interval	(2-Sided) 95% 0.675 to 1.258
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Arm C (Bevacizumab+Paclitaxel+Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Pain in Chest in ITT-WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.3134
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.829
	Confidence Interval	(2-Sided) 95% 0.576 to 1.194
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
	Comments	Pain in Chest in ITT-WT Population
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis

Statistical Test of Hypothesis	p-Value	0.6115
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.910
	Confidence Interval	(2-Sided) 95% 0.633 to 1.309
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale
Description	The SILC (Symptoms in Lung Cancer) scale was used to assess patient-reported severity of lung cancer symptoms (chest pain, dyspnea, and cough). The SILC scale is a 9-item content validated self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a symptom severity score. The SILC questionnaire comprises three individual symptoms (dyspnea, cough, chest pain) and are scored at the individual symptom level, thus have a dyspnea score, chest pain score, and cough score. Each individual symptom score is calculated as the average of responses for the symptom items [e.g. Chest Pain Score=mean (item 1; item 2)]. An increase in score is suggestive of a worsening in symptomology (i.e. frequency or severity). A score change of ≥0.3 points for the dyspnea and cough symptom scores is considered to be clinically significant; whereas a score change of ≥0.5 points for the chest pain score is considered to be clinically significant.
Time Frame	Baseline up to approximately 29 months

Outcome Measure Data

Analysis Population Description
No participants were analyzed due to psychometric properties within the NSCLC population are still being determined. Due to quality issues data not analyzed.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	0	0	0

20. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Description	Percentage of participants with at least one adverse event.
Time Frame	Baseline up to data cutoff date 7 December 2020 (up to approximately 68 months)

Outcome Measure Data

Analysis Population Description
Safety population included all treated patients, defined as randomized patients who received any amount of any component of study treatment.

Arm/Group Title	Arm C (Bevacizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm A (Atezolizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.
Measure Participants	394	393	400
Number [Percentage]	99.0	98.2	97.8

21. Secondary Outcome

Title	Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Description
Time Frame	Baseline up to approximately 29 months

Outcome Measure Data

Analysis Population Description
The baseline ADA-evaluable population for each study treatment included patients who had a baseline ADA result. The post-baseline ADA-evaluable population for each study treatment included patients who had at least one post-baseline ADA result and had received at least on dose of that study treatment.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
Measure Participants	389	376
Number [Percentage of Participants]	4.6 1.2%	2.9 0.7%

22. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Arm A and Arm B
Description	The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes.
Time Frame	Day 1 of Cycle 1 and 3 (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description
The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
Measure Participants	378	364
Cycle 1 Day 1	410 (157)	414 (127)
Cycle 3 Day 1	498 (160)	540 (198)

23. Secondary Outcome

Title	Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Arm A and Arm B
Description
Time Frame	Day 21 of Cycles 1, 2 3, and 7 (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description
The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
Measure Participants	354	345
Cycle 1 Day 21	76.4 (37.7)	80.8 (41.4)
Cycle 2 Day 21	119 (55.7)	130 (57.1)
Cycle 3 Day 21	146 (58.9)	160 (102)
Cycle 7 Day 21	219 (89.6)	220 (99.0)

24. Secondary Outcome

Title	Plasma Concentrations for Carboplatin in Arm A, Arm B, and Arm C
Description
Time Frame	Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 h after carboplatin infusion (infusion duration=15 to 30 minutes) on D1 of Cy1,3 (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description
The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	28	35	24
Cy1D1 Pre-dose	NA (NA)	NA (NA)	NA (NA)
Cy1D1 Before End of Infusion	18300 (9610)	18300 (11900)	17200 (9860)
Cy1D1 After Infusion	11700 (5570)	13900 (14300)	10100 (5320)
Cy2D21	176 (82.9)	190 (113)	143 (73.0)
Cy3D1 Before End of Infusion	20900 (8330)	18700 (9410)	20600 (12900)
Cy3D1 After Infusion	11700 (6990)	12200 (7480)	10400 (4150)

25. Secondary Outcome

Title	Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C
Description
Time Frame	Predose (same day of treatment administration), 5-10 minutes before end of paclitaxel infusion, 1 h after paclitaxel infusion (infusion duration=3 h) on D1 of Cy1,3 (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description
The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

Arm/Group Title	Arm A (Atezolizumab+Paclitaxel+Carboplatin)	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received intravenous (IV) infusion of atezolizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab during maintenance treatment phase until loss of clinical benefit.	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	28	35	24
Cy1D1 Pre-dose	NA (NA)	NA (NA)	NA (NA)
Cy1D1 Before End of Infusion	4850 (2800)	6440 (3640)	5560 (2590)
Cy1D1 After Infusion	2300 (2790)	2490 (3020)	1980 (1780)
Cy2D21	NA (NA)	NA (NA)
Cy3D1 Before End Of Infusion	5810 (3610)	7810 (4510)	7810 (5160)
Cy3D1 After Infusion	1800 (1660)	2990 (5830)	1930 (1380)

26. Secondary Outcome

Title	Cmax of Bevacizumab in Arm B and Arm C
Description
Time Frame	Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description
The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

Arm/Group Title	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	205	215
Cycle 1 Day 1	329 (129)	323 (95.0)
Cycle 3 Day 1	413 (126)	430 (123)

27. Secondary Outcome

Title	Cmin of Bevacizumab in Arm B and Arm C
Description
Time Frame	Cycle 1 Day 1 and Cycle 2 Day 21 (Cycle length=21 days)

Outcome Measure Data

Analysis Population Description
The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab, bevacizumab, carboplatin, or paclitaxel and who had evaluable PK samples post-dose.

Arm/Group Title	Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)	Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Arm/Group Description	Participants received IV infusion of atezolizumab and bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of atezolizumab until loss of clinical benefit and bevacizumab until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.	Participants received IV infusion of bevacizumab on Day 1 of each 21-day cycle followed by IV infusion of paclitaxel and carboplatin on Day 1 of each 21-day cycle for 4 or 6 cycles or loss of clinical benefit whichever occurs first, during induction treatment phase. Participants received IV infusion of bevacizumab during maintenance treatment phase until progressive disease, unacceptable toxicity, or death.
Measure Participants	325	348
Cycle 1 Day 1	NA (NA)	NA (NA)
Cycle 2 Day 21	98.0 (50.9)	90.4 (36.8)

Adverse Events

	Arm C (Bev+CP)		Arm B (Atezo+Bev+CP)		Arm A (Atezo+CP)
Time Frame	From the first study drug to the data cutoff date 7 December 2020 (up to approximately 68 months)
Adverse Event Reporting Description	The safety population included all treated participants, defined as randomized participants who received any amount of any component of study treatment.

Arm/Group Title	Arm C (Bev+CP)		Arm B (Atezo+Bev+CP)		Arm A (Atezo+CP)
Arm/Group Description	Bevacizumab+Paclitaxel+Carboplatin		Atezolizumab+Bevacizumab+Paclitaxel+Carboplatin		Atezolizumab+Paclitaxel+Carboplatin
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	311/394 (78.9%)		285/393 (72.5%)		293/400 (73.3%)
Serious Adverse Events
	Arm C (Bev+CP)		Arm B (Atezo+Bev+CP)		Arm A (Atezo+CP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	142/394 (36%)		190/393 (48.3%)		170/400 (42.5%)
Blood and lymphatic system disorders
ANAEMIA	4/394 (1%)	4	5/393 (1.3%)	5	5/400 (1.3%)	6
BONE MARROW FAILURE	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
FEBRILE NEUTROPENIA	17/394 (4.3%)	18	27/393 (6.9%)	30	13/400 (3.3%)	13
LEUKOPENIA	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
MYELOSUPPRESSION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
NEUTROPENIA	2/394 (0.5%)	2	4/393 (1%)	4	1/400 (0.3%)	1
NORMOCHROMIC ANAEMIA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
PANCYTOPENIA	2/394 (0.5%)	2	1/393 (0.3%)	1	0/400 (0%)	0
SPONTANEOUS HAEMATOMA	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
THROMBOCYTOPENIA	2/394 (0.5%)	2	6/393 (1.5%)	6	1/400 (0.3%)	1
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	3/394 (0.8%)	3	2/393 (0.5%)	2	1/400 (0.3%)	1
ATRIAL FIBRILLATION	1/394 (0.3%)	1	2/393 (0.5%)	2	2/400 (0.5%)	2
ATRIAL FLUTTER	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
ATRIOVENTRICULAR BLOCK SECOND DEGREE	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
AUTOIMMUNE MYOCARDITIS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
CARDIAC ARREST	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
CARDIAC FAILURE	1/394 (0.3%)	1	2/393 (0.5%)	2	0/400 (0%)	0
CARDIAC FAILURE CONGESTIVE	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
CORONARY ARTERY DISEASE	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
LEFT VENTRICULAR DYSFUNCTION	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
MYOCARDIAL INFARCTION	1/394 (0.3%)	1	1/393 (0.3%)	3	2/400 (0.5%)	2
MYOCARDIAL ISCHAEMIA	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
PERICARDIAL EFFUSION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
PERICARDITIS	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
TACHYARRHYTHMIA	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
VENTRICULAR TACHYCARDIA	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
Endocrine disorders
ADRENAL INSUFFICIENCY	1/394 (0.3%)	1	2/393 (0.5%)	2	1/400 (0.3%)	1
ADRENOCORTICAL INSUFFICIENCY ACUTE	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
DIABETES INSIPIDUS	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
HYPOPHYSITIS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
HYPOTHYROIDISM	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
SECONDARY ADRENOCORTICAL INSUFFICIENCY	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
Eye disorders
OPTIC NEUROPATHY	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
Gastrointestinal disorders
ABDOMINAL PAIN	3/394 (0.8%)	3	1/393 (0.3%)	1	2/400 (0.5%)	2
ABDOMINAL PAIN LOWER	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
ABDOMINAL PAIN UPPER	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
COLITIS	0/394 (0%)	0	6/393 (1.5%)	6	1/400 (0.3%)	1
COLITIS ISCHAEMIC	2/394 (0.5%)	2	1/393 (0.3%)	1	0/400 (0%)	0
CONSTIPATION	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
DIARRHOEA	3/394 (0.8%)	3	10/393 (2.5%)	11	8/400 (2%)	8
DIVERTICULAR PERFORATION	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
DUODENAL ULCER	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
DYSPHAGIA	0/394 (0%)	0	1/393 (0.3%)	1	2/400 (0.5%)	3
FAECALOMA	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
FOOD POISONING	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
GASTRIC HAEMORRHAGE	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
GASTRITIS	0/394 (0%)	0	4/393 (1%)	4	0/400 (0%)	0
GASTROINTESTINAL HAEMORRHAGE	0/394 (0%)	0	1/393 (0.3%)	1	2/400 (0.5%)	2
GLOSSODYNIA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
ILEUS PARALYTIC	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
INGUINAL HERNIA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
INTESTINAL ANGINA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
INTESTINAL HAEMORRHAGE	0/394 (0%)	0	1/393 (0.3%)	2	0/400 (0%)	0
INTESTINAL INFARCTION	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
INTESTINAL ISCHAEMIA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
INTESTINAL OBSTRUCTION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
INTESTINAL PERFORATION	2/394 (0.5%)	2	0/393 (0%)	0	0/400 (0%)	0
IRRITABLE BOWEL SYNDROME	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
LARGE INTESTINAL HAEMORRHAGE	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
LARGE INTESTINE PERFORATION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
NAUSEA	3/394 (0.8%)	3	7/393 (1.8%)	7	1/400 (0.3%)	1
OESOPHAGEAL FOOD IMPACTION	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
PANCREATITIS ACUTE	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
VOMITING	3/394 (0.8%)	3	5/393 (1.3%)	5	4/400 (1%)	5
General disorders
ASTHENIA	1/394 (0.3%)	1	0/393 (0%)	0	1/400 (0.3%)	1
CATHETER SITE ERYTHEMA	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
CHEST PAIN	6/394 (1.5%)	7	4/393 (1%)	4	1/400 (0.3%)	2
COMPLICATION ASSOCIATED WITH DEVICE	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
DEATH	2/394 (0.5%)	2	2/393 (0.5%)	2	1/400 (0.3%)	1
GENERAL PHYSICAL HEALTH DETERIORATION	2/394 (0.5%)	2	2/393 (0.5%)	2	0/400 (0%)	0
INFLUENZA LIKE ILLNESS	1/394 (0.3%)	1	0/393 (0%)	0	1/400 (0.3%)	1
INFUSION SITE EXTRAVASATION	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
MUCOSAL INFLAMMATION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
NON-CARDIAC CHEST PAIN	1/394 (0.3%)	1	1/393 (0.3%)	1	0/400 (0%)	0
OEDEMA PERIPHERAL	1/394 (0.3%)	1	1/393 (0.3%)	1	0/400 (0%)	0
PAIN	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
PYREXIA	1/394 (0.3%)	1	8/393 (2%)	8	6/400 (1.5%)	6
Hepatobiliary disorders
CHOLANGITIS	1/394 (0.3%)	1	3/393 (0.8%)	3	0/400 (0%)	0
CHOLANGITIS ACUTE	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
CHOLELITHIASIS	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
HEPATITIS	0/394 (0%)	0	2/393 (0.5%)	2	1/400 (0.3%)	1
HEPATOMEGALY	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
HEPATOTOXICITY	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
Immune system disorders
ANAPHYLACTIC REACTION	0/394 (0%)	0	0/393 (0%)	0	2/400 (0.5%)	2
DRUG HYPERSENSITIVITY	0/394 (0%)	0	1/393 (0.3%)	2	2/400 (0.5%)	2
HYPERSENSITIVITY	2/394 (0.5%)	2	1/393 (0.3%)	2	1/400 (0.3%)	1
Infections and infestations
ABDOMINAL SEPSIS	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
ANAL ABSCESS	1/394 (0.3%)	1	1/393 (0.3%)	1	1/400 (0.3%)	1
BACTERAEMIA	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
BACTERIAL INFECTION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
BONE ABSCESS	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
BRONCHITIS	2/394 (0.5%)	2	4/393 (1%)	4	1/400 (0.3%)	1
BURSITIS INFECTIVE	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
CELLULITIS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
CHRONIC SINUSITIS	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
CLOSTRIDIUM DIFFICILE INFECTION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
DEVICE RELATED INFECTION	0/394 (0%)	0	0/393 (0%)	0	2/400 (0.5%)	2
DIVERTICULITIS	1/394 (0.3%)	1	1/393 (0.3%)	2	1/400 (0.3%)	1
EMPYEMA	0/394 (0%)	0	0/393 (0%)	0	2/400 (0.5%)	2
ENCEPHALITIS	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
ENDOCARDITIS BACTERIAL	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
ENTERITIS INFECTIOUS	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
ENTEROCOLITIS BACTERIAL	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
FEBRILE INFECTION	1/394 (0.3%)	1	0/393 (0%)	0	1/400 (0.3%)	1
GASTROENTERITIS	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
GASTROENTERITIS CLOSTRIDIAL	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
HAEMORRHAGIC PNEUMONIA	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
HEPATITIS A	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
HEPATITIS C	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
HERPES ZOSTER	0/394 (0%)	0	0/393 (0%)	0	2/400 (0.5%)	2
INFECTED SKIN ULCER	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
INFECTION	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
INFECTIOUS PLEURAL EFFUSION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
INFLUENZA	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
KLEBSIELLA SEPSIS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
LARGE INTESTINE INFECTION	0/394 (0%)	0	2/393 (0.5%)	2	0/400 (0%)	0
LOWER RESPIRATORY TRACT INFECTION	0/394 (0%)	0	1/393 (0.3%)	1	3/400 (0.8%)	4
NEUTROPENIC SEPSIS	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
OSTEOMYELITIS	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
PARAINFLUENZAE VIRUS INFECTION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
PAROTITIS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
PNEUMONIA	18/394 (4.6%)	19	28/393 (7.1%)	30	21/400 (5.3%)	23
PNEUMONIA ADENOVIRAL	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
PNEUMONIA BACTERIAL	0/394 (0%)	0	3/393 (0.8%)	3	0/400 (0%)	0
PROSTATIC ABSCESS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
PYOPNEUMOTHORAX	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
RESPIRATORY SYNCYTIAL VIRUS BRONCHITIS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
RESPIRATORY SYNCYTIAL VIRUS INFECTION	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
RESPIRATORY TRACT INFECTION	3/394 (0.8%)	3	4/393 (1%)	4	2/400 (0.5%)	2
RESPIRATORY TRACT INFECTION FUNGAL	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
SALMONELLOSIS	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
SCROTAL ABSCESS	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
SEPSIS	5/394 (1.3%)	5	3/393 (0.8%)	4	3/400 (0.8%)	3
SEPTIC SHOCK	0/394 (0%)	0	2/393 (0.5%)	2	2/400 (0.5%)	2
STAPHYLOCOCCAL BACTERAEMIA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
STAPHYLOCOCCAL INFECTION	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
TOOTH ABSCESS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
UPPER RESPIRATORY TRACT INFECTION	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
URINARY TRACT INFECTION	3/394 (0.8%)	3	3/393 (0.8%)	3	4/400 (1%)	4
VASCULAR DEVICE INFECTION	0/394 (0%)	0	2/393 (0.5%)	2	1/400 (0.3%)	1
VIRAL INFECTION	0/394 (0%)	0	3/393 (0.8%)	3	0/400 (0%)	0
Injury, poisoning and procedural complications
ACCIDENTAL OVERDOSE	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
FALL	0/394 (0%)	0	2/393 (0.5%)	2	0/400 (0%)	0
FEMUR FRACTURE	1/394 (0.3%)	1	1/393 (0.3%)	1	2/400 (0.5%)	2
FRACTURE	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
HIP FRACTURE	0/394 (0%)	0	2/393 (0.5%)	2	2/400 (0.5%)	2
HUMERUS FRACTURE	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
INFUSION RELATED REACTION	0/394 (0%)	0	1/393 (0.3%)	1	3/400 (0.8%)	3
PROCEDURAL COMPLICATION	0/394 (0%)	0	2/393 (0.5%)	2	0/400 (0%)	0
PROCEDURAL PAIN	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
RIB FRACTURE	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
SPINAL COMPRESSION FRACTURE	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
STERNAL FRACTURE	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
WOUND COMPLICATION	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
ASPARTATE AMINOTRANSFERASE INCREASED	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
BLOOD LACTATE DEHYDROGENASE INCREASED	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
BLOOD PRESSURE INCREASED	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
C-REACTIVE PROTEIN INCREASED	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
GENERAL PHYSICAL CONDITION ABNORMAL	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
HEPATIC ENZYME INCREASED	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
LIPASE INCREASED	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
NEUTROPHIL COUNT DECREASED	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
PLATELET COUNT DECREASED	2/394 (0.5%)	2	2/393 (0.5%)	2	0/400 (0%)	0
TRANSAMINASES INCREASED	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
TROPONIN INCREASED	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
WEIGHT DECREASED	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
WHITE BLOOD CELL COUNT DECREASED	1/394 (0.3%)	1	2/393 (0.5%)	2	0/400 (0%)	0
Metabolism and nutrition disorders
DECREASED APPETITE	0/394 (0%)	0	2/393 (0.5%)	2	0/400 (0%)	0
DEHYDRATION	6/394 (1.5%)	6	7/393 (1.8%)	9	3/400 (0.8%)	3
FAILURE TO THRIVE	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
HYPERCALCAEMIA	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
HYPERGLYCAEMIA	1/394 (0.3%)	2	0/393 (0%)	0	0/400 (0%)	0
HYPOKALAEMIA	0/394 (0%)	0	2/393 (0.5%)	2	1/400 (0.3%)	1
HYPONATRAEMIA	1/394 (0.3%)	1	2/393 (0.5%)	2	1/400 (0.3%)	1
HYPOPHOSPHATAEMIA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA	2/394 (0.5%)	2	2/393 (0.5%)	2	3/400 (0.8%)	3
BACK PAIN	3/394 (0.8%)	3	2/393 (0.5%)	2	1/400 (0.3%)	1
BONE PAIN	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
COMPARTMENT SYNDROME	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
FLANK PAIN	0/394 (0%)	0	0/393 (0%)	0	2/400 (0.5%)	2
MUSCULAR WEAKNESS	1/394 (0.3%)	1	1/393 (0.3%)	1	0/400 (0%)	0
MUSCULOSKELETAL CHEST PAIN	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
MYALGIA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
OSTEOLYSIS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
PAIN IN EXTREMITY	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
SOFT TISSUE NECROSIS	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
SPINAL PAIN	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
VERTEBRAL FORAMINAL STENOSIS	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ADENOCARCINOMA GASTRIC	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
B-CELL LYMPHOMA	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
BLADDER NEOPLASM	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
BLADDER TRANSITIONAL CELL CARCINOMA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
MARROW HYPERPLASIA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
MENINGIOMA	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
METASTASES TO MENINGES	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
TUMOUR PAIN	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
TUMOUR PSEUDOPROGRESSION	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
Nervous system disorders
ATAXIA	1/394 (0.3%)	1	0/393 (0%)	0	1/400 (0.3%)	1
CEREBRAL HAEMORRHAGE	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
CEREBRAL INFARCTION	1/394 (0.3%)	1	1/393 (0.3%)	1	1/400 (0.3%)	1
CEREBRAL ISCHAEMIA	0/394 (0%)	0	2/393 (0.5%)	2	1/400 (0.3%)	1
CEREBROVASCULAR ACCIDENT	1/394 (0.3%)	1	5/393 (1.3%)	5	2/400 (0.5%)	2
COGNITIVE DISORDER	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
DEPRESSED LEVEL OF CONSCIOUSNESS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
DIZZINESS	1/394 (0.3%)	1	1/393 (0.3%)	1	0/400 (0%)	0
DIZZINESS POSTURAL	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
DYSAESTHESIA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
ENCEPHALOPATHY	1/394 (0.3%)	1	0/393 (0%)	0	1/400 (0.3%)	1
FOCAL DYSCOGNITIVE SEIZURES	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
HAEMORRHAGE INTRACRANIAL	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
HEADACHE	0/394 (0%)	0	2/393 (0.5%)	2	0/400 (0%)	0
HEMIPARESIS	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
ISCHAEMIC STROKE	4/394 (1%)	4	1/393 (0.3%)	1	2/400 (0.5%)	2
LOSS OF CONSCIOUSNESS	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
METABOLIC ENCEPHALOPATHY	1/394 (0.3%)	1	1/393 (0.3%)	1	0/400 (0%)	0
NEUROPATHY PERIPHERAL	1/394 (0.3%)	1	1/393 (0.3%)	1	0/400 (0%)	0
PARTIAL SEIZURES	0/394 (0%)	0	0/393 (0%)	0	2/400 (0.5%)	2
PERIPHERAL SENSORY NEUROPATHY	2/394 (0.5%)	2	0/393 (0%)	0	1/400 (0.3%)	1
POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME	2/394 (0.5%)	2	0/393 (0%)	0	0/400 (0%)	0
PRESYNCOPE	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
SEIZURE	1/394 (0.3%)	1	5/393 (1.3%)	5	2/400 (0.5%)	3
SOMNOLENCE	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
SPINAL CORD COMPRESSION	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
SYNCOPE	2/394 (0.5%)	2	1/393 (0.3%)	1	1/400 (0.3%)	1
TRANSIENT ISCHAEMIC ATTACK	1/394 (0.3%)	1	2/393 (0.5%)	2	0/400 (0%)	0
Psychiatric disorders
ALCOHOL WITHDRAWAL SYNDROME	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
ANXIETY	1/394 (0.3%)	1	1/393 (0.3%)	2	0/400 (0%)	0
BIPOLAR DISORDER	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
CONFUSIONAL STATE	2/394 (0.5%)	2	1/393 (0.3%)	1	1/400 (0.3%)	1
DELIRIUM	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
DELUSION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
MENTAL STATUS CHANGES	1/394 (0.3%)	1	1/393 (0.3%)	1	0/400 (0%)	0
PSYCHOTIC DISORDER	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
SUICIDAL IDEATION	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
Renal and urinary disorders
ACUTE KIDNEY INJURY	3/394 (0.8%)	3	3/393 (0.8%)	3	2/400 (0.5%)	2
GLOMERULONEPHROPATHY	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
HAEMATURIA	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
NEPHROLITHIASIS	0/394 (0%)	0	2/393 (0.5%)	2	0/400 (0%)	0
PRERENAL FAILURE	0/394 (0%)	0	2/393 (0.5%)	2	0/400 (0%)	0
RENAL FAILURE	0/394 (0%)	0	3/393 (0.8%)	3	0/400 (0%)	0
RENAL IMPAIRMENT	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	2
RENAL INJURY	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
TUBULOINTERSTITIAL NEPHRITIS	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
URINARY TRACT OBSTRUCTION	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
ACUTE RESPIRATORY FAILURE	0/394 (0%)	0	1/393 (0.3%)	1	3/400 (0.8%)	3
BRONCHOSTENOSIS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	2/394 (0.5%)	2	3/393 (0.8%)	3	3/400 (0.8%)	3
COUGH	0/394 (0%)	0	3/393 (0.8%)	3	0/400 (0%)	0
DYSPNOEA	6/394 (1.5%)	6	2/393 (0.5%)	2	4/400 (1%)	4
EPISTAXIS	1/394 (0.3%)	1	1/393 (0.3%)	2	0/400 (0%)	0
HAEMOPTYSIS	2/394 (0.5%)	2	8/393 (2%)	8	3/400 (0.8%)	4
HICCUPS	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
HYPOXIA	1/394 (0.3%)	1	2/393 (0.5%)	2	2/400 (0.5%)	2
IMMUNE-MEDIATED PNEUMONITIS	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
INTERSTITIAL LUNG DISEASE	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
PLEURAL EFFUSION	2/394 (0.5%)	2	0/393 (0%)	0	3/400 (0.8%)	3
PLEURISY	0/394 (0%)	0	1/393 (0.3%)	2	1/400 (0.3%)	1
PLEURITIC PAIN	1/394 (0.3%)	3	0/393 (0%)	0	0/400 (0%)	0
PNEUMONIA ASPIRATION	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
PNEUMONITIS	0/394 (0%)	0	7/393 (1.8%)	7	8/400 (2%)	8
PNEUMOTHORAX	2/394 (0.5%)	3	0/393 (0%)	0	4/400 (1%)	4
PULMONARY EMBOLISM	8/394 (2%)	8	5/393 (1.3%)	5	8/400 (2%)	8
PULMONARY HAEMORRHAGE	4/394 (1%)	4	2/393 (0.5%)	2	0/400 (0%)	0
PULMONARY NECROSIS	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
PULMONARY OEDEMA	0/394 (0%)	0	0/393 (0%)	0	2/400 (0.5%)	2
RESPIRATORY FAILURE	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
Skin and subcutaneous tissue disorders
DERMATITIS	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
ERYTHEMA MULTIFORME	0/394 (0%)	0	0/393 (0%)	0	3/400 (0.8%)	3
PEMPHIGOID	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
RASH	0/394 (0%)	0	1/393 (0.3%)	2	3/400 (0.8%)	3
RASH MACULO-PAPULAR	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
Surgical and medical procedures
VERTEBROPLASTY	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
Vascular disorders
ANEURYSM	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
AORTIC DISSECTION	0/394 (0%)	0	2/393 (0.5%)	2	0/400 (0%)	0
ARTERIAL OCCLUSIVE DISEASE	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
DEEP VEIN THROMBOSIS	1/394 (0.3%)	1	2/393 (0.5%)	2	1/400 (0.3%)	1
DIABETIC VASCULAR DISORDER	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
EMBOLISM	0/394 (0%)	0	0/393 (0%)	0	2/400 (0.5%)	2
EMBOLISM VENOUS	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
HAEMATOMA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
HYPERTENSION	1/394 (0.3%)	1	1/393 (0.3%)	1	0/400 (0%)	0
HYPOTENSION	0/394 (0%)	0	2/393 (0.5%)	2	1/400 (0.3%)	1
LYMPHOEDEMA	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
ORTHOSTATIC HYPOTENSION	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
PERIPHERAL ARTERY THROMBOSIS	0/394 (0%)	0	1/393 (0.3%)	1	0/400 (0%)	0
PERIPHERAL ISCHAEMIA	0/394 (0%)	0	1/393 (0.3%)	1	1/400 (0.3%)	1
PERIPHERAL VASCULAR DISORDER	1/394 (0.3%)	1	0/393 (0%)	0	0/400 (0%)	0
THROMBOSIS	1/394 (0.3%)	1	2/393 (0.5%)	2	1/400 (0.3%)	1
VENOUS THROMBOSIS LIMB	0/394 (0%)	0	0/393 (0%)	0	1/400 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Arm C (Bev+CP)		Arm B (Atezo+Bev+CP)		Arm A (Atezo+CP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	381/394 (96.7%)		375/393 (95.4%)		385/400 (96.3%)
Blood and lymphatic system disorders
ANAEMIA	104/394 (26.4%)	124	116/393 (29.5%)	134	146/400 (36.5%)	183
LEUKOPENIA	14/394 (3.6%)	17	14/393 (3.6%)	20	20/400 (5%)	35
NEUTROPENIA	70/394 (17.8%)	107	72/393 (18.3%)	111	60/400 (15%)	85
THROMBOCYTOPENIA	45/394 (11.4%)	64	53/393 (13.5%)	74	49/400 (12.3%)	78
Endocrine disorders
HYPOTHYROIDISM	13/394 (3.3%)	13	50/393 (12.7%)	56	33/400 (8.3%)	40
Gastrointestinal disorders
ABDOMINAL PAIN	20/394 (5.1%)	24	36/393 (9.2%)	48	29/400 (7.3%)	36
CONSTIPATION	92/394 (23.4%)	115	122/393 (31%)	151	103/400 (25.8%)	128
DIARRHOEA	98/394 (24.9%)	133	125/393 (31.8%)	221	82/400 (20.5%)	137
DRY MOUTH	6/394 (1.5%)	6	20/393 (5.1%)	22	13/400 (3.3%)	16
GASTROOESOPHAGEAL REFLUX DISEASE	9/394 (2.3%)	11	20/393 (5.1%)	20	11/400 (2.8%)	13
NAUSEA	124/394 (31.5%)	177	149/393 (37.9%)	223	130/400 (32.5%)	210
STOMATITIS	24/394 (6.1%)	30	54/393 (13.7%)	73	23/400 (5.8%)	27
VOMITING	67/394 (17%)	105	71/393 (18.1%)	99	69/400 (17.3%)	92
General disorders
ASTHENIA	80/394 (20.3%)	107	84/393 (21.4%)	143	76/400 (19%)	127
CHEST PAIN	28/394 (7.1%)	32	35/393 (8.9%)	37	38/400 (9.5%)	44
FATIGUE	107/394 (27.2%)	125	137/393 (34.9%)	157	111/400 (27.8%)	129
MALAISE	11/394 (2.8%)	13	27/393 (6.9%)	43	20/400 (5%)	27
MUCOSAL INFLAMMATION	24/394 (6.1%)	27	38/393 (9.7%)	42	10/400 (2.5%)	10
OEDEMA PERIPHERAL	19/394 (4.8%)	20	35/393 (8.9%)	42	29/400 (7.3%)	33
PAIN	17/394 (4.3%)	17	26/393 (6.6%)	31	22/400 (5.5%)	23
PYREXIA	34/394 (8.6%)	44	67/393 (17%)	88	53/400 (13.3%)	66
Infections and infestations
BRONCHITIS	16/394 (4.1%)	17	28/393 (7.1%)	37	15/400 (3.8%)	16
NASOPHARYNGITIS	17/394 (4.3%)	18	27/393 (6.9%)	34	31/400 (7.8%)	50
PNEUMONIA	15/394 (3.8%)	17	19/393 (4.8%)	22	21/400 (5.3%)	23
UPPER RESPIRATORY TRACT INFECTION	16/394 (4.1%)	20	37/393 (9.4%)	56	24/400 (6%)	43
URINARY TRACT INFECTION	28/394 (7.1%)	37	35/393 (8.9%)	57	37/400 (9.3%)	51
Investigations
ALANINE AMINOTRANSFERASE INCREASED	20/394 (5.1%)	24	30/393 (7.6%)	45	22/400 (5.5%)	26
ASPARTATE AMINOTRANSFERASE INCREASED	18/394 (4.6%)	19	30/393 (7.6%)	48	22/400 (5.5%)	29
NEUTROPHIL COUNT DECREASED	34/394 (8.6%)	72	49/393 (12.5%)	87	33/400 (8.3%)	64
PLATELET COUNT DECREASED	44/394 (11.2%)	76	57/393 (14.5%)	84	41/400 (10.3%)	59
WEIGHT DECREASED	42/394 (10.7%)	46	52/393 (13.2%)	56	29/400 (7.3%)	32
WHITE BLOOD CELL COUNT DECREASED	20/394 (5.1%)	39	26/393 (6.6%)	42	17/400 (4.3%)	27
Metabolism and nutrition disorders
DECREASED APPETITE	86/394 (21.8%)	102	119/393 (30.3%)	157	100/400 (25%)	129
DEHYDRATION	15/394 (3.8%)	16	33/393 (8.4%)	42	7/400 (1.8%)	7
HYPOKALAEMIA	16/394 (4.1%)	18	36/393 (9.2%)	47	24/400 (6%)	30
HYPOMAGNESAEMIA	25/394 (6.3%)	29	55/393 (14%)	76	38/400 (9.5%)	49
HYPONATRAEMIA	17/394 (4.3%)	20	23/393 (5.9%)	32	13/400 (3.3%)	14
Musculoskeletal and connective tissue disorders
ARTHRALGIA	102/394 (25.9%)	155	130/393 (33.1%)	227	105/400 (26.3%)	175
BACK PAIN	43/394 (10.9%)	50	57/393 (14.5%)	67	51/400 (12.8%)	70
BONE PAIN	19/394 (4.8%)	19	23/393 (5.9%)	33	16/400 (4%)	18
MUSCLE SPASMS	7/394 (1.8%)	8	20/393 (5.1%)	24	10/400 (2.5%)	10
MYALGIA	53/394 (13.5%)	81	69/393 (17.6%)	118	67/400 (16.8%)	104
PAIN IN EXTREMITY	32/394 (8.1%)	43	50/393 (12.7%)	63	45/400 (11.3%)	52
Nervous system disorders
DIZZINESS	26/394 (6.6%)	31	27/393 (6.9%)	34	28/400 (7%)	39
DYSGEUSIA	19/394 (4.8%)	24	24/393 (6.1%)	27	15/400 (3.8%)	16
HEADACHE	53/394 (13.5%)	65	70/393 (17.8%)	87	41/400 (10.3%)	49
NEUROPATHY PERIPHERAL	67/394 (17%)	77	92/393 (23.4%)	105	104/400 (26%)	117
PARAESTHESIA	44/394 (11.2%)	50	53/393 (13.5%)	59	37/400 (9.3%)	42
PERIPHERAL SENSORY NEUROPATHY	54/394 (13.7%)	59	65/393 (16.5%)	73	58/400 (14.5%)	65
Psychiatric disorders
ANXIETY	22/394 (5.6%)	23	31/393 (7.9%)	31	23/400 (5.8%)	23
DEPRESSION	13/394 (3.3%)	13	25/393 (6.4%)	26	15/400 (3.8%)	16
INSOMNIA	38/394 (9.6%)	41	42/393 (10.7%)	43	50/400 (12.5%)	56
Renal and urinary disorders
PROTEINURIA	63/394 (16%)	81	80/393 (20.4%)	128	9/400 (2.3%)	13
Respiratory, thoracic and mediastinal disorders
COUGH	77/394 (19.5%)	94	86/393 (21.9%)	107	82/400 (20.5%)	99
DYSPHONIA	18/394 (4.6%)	19	27/393 (6.9%)	27	11/400 (2.8%)	12
DYSPNOEA	60/394 (15.2%)	66	67/393 (17%)	81	86/400 (21.5%)	107
EPISTAXIS	86/394 (21.8%)	108	67/393 (17%)	89	17/400 (4.3%)	22
HAEMOPTYSIS	18/394 (4.6%)	21	21/393 (5.3%)	24	16/400 (4%)	27
OROPHARYNGEAL PAIN	10/394 (2.5%)	10	22/393 (5.6%)	25	9/400 (2.3%)	10
Skin and subcutaneous tissue disorders
ALOPECIA	180/394 (45.7%)	183	188/393 (47.8%)	195	180/400 (45%)	182
DRY SKIN	9/394 (2.3%)	9	29/393 (7.4%)	31	24/400 (6%)	28
PRURITUS	25/394 (6.3%)	29	58/393 (14.8%)	76	52/400 (13%)	72
RASH	28/394 (7.1%)	34	72/393 (18.3%)	92	71/400 (17.8%)	94
Vascular disorders
HYPERTENSION	87/394 (22.1%)	102	104/393 (26.5%)	149	16/400 (4%)	16

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.

Results Point of Contact

Name/Title	Medical Communications
Organization	Hoffmann-La Roche
Phone	800-821-8590
Email	genentech@druginfo.com

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT02366143

Other Study ID Numbers:

GO29436
2014-003207-30

First Posted:

Feb 19, 2015

Last Update Posted:

Sep 23, 2021

Last Verified:

Aug 1, 2021