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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) (IMpower150)

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ClinicalTrials.gov Identifier: NCT02366143
Recruitment Status : Completed
First Posted : February 19, 2015
Results First Posted : October 27, 2020
Last Update Posted : October 27, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Non-Small-Cell Lung
Interventions Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Drug: Bevacizumab
Drug: Carboplatin
Drug: Paclitaxel
Enrollment 1202
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm B Arm A Arm C
Hide Arm/Group Description Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin Atezolizumab+Paclitaxel+Carboplatin Bevacizumab+Paclitaxel+Carboplatin
Period Title: Overall Study
Started 400 402 400
Completed 0 0 0
Not Completed 400 402 400
Reason Not Completed
Death             272             275             301
Lost to Follow-up             2             1             1
Physician Decision             2             1             1
Protocol Violation             0             2             0
Withdrawal by Subject             15             21             16
On-Going in Study             107             101             79
Increased Microscopic RBCS on Urinalysis             1             0             0
Randomization Error             0             0             1
PI Move and Site Closure             0             1             1
Ineligible             1             0             0
Arm/Group Title Arm B Arm A Arm C Total
Hide Arm/Group Description Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin Atezolizumab+Paclitaxel+Carboplatin Bevacizumab+Paclitaxel+Carboplatin Total of all reporting groups
Overall Number of Baseline Participants 400 402 400 1202
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 400 participants 402 participants 400 participants 1202 participants
63.0  (9.5) 62.3  (9.2) 63.1  (9.3) 62.8  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 400 participants 402 participants 400 participants 1202 participants
Female
160
  40.0%
161
  40.0%
161
  40.3%
482
  40.1%
Male
240
  60.0%
241
  60.0%
239
  59.8%
720
  59.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 400 participants 402 participants 400 participants 1202 participants
American Indian or Alaska Native
3
   0.8%
0
   0.0%
1
   0.3%
4
   0.3%
Asian
56
  14.0%
48
  11.9%
46
  11.5%
150
  12.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   0.8%
9
   2.2%
12
   3.0%
24
   2.0%
White
322
  80.5%
331
  82.3%
335
  83.8%
988
  82.2%
More than one race
3
   0.8%
4
   1.0%
0
   0.0%
7
   0.6%
Unknown or Not Reported
13
   3.3%
10
   2.5%
6
   1.5%
29
   2.4%
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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 356 336
Median (95% Confidence Interval)
Unit of Measure: Months
Teff-high WT Population Number Analyzed 155 participants 129 participants
11.3
(9.1 to 13.0)
6.8
(5.9 to 7.4)
ITT-WT Population Number Analyzed 356 participants 336 participants
8.3
(7.7 to 9.8)
6.8
(6.0 to 7.1)
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.52 to 0.74
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.38 to 0.68
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 359 337
Median (95% Confidence Interval)
Unit of Measure: Months
19.2
(17.0 to 23.8)
14.7
(13.3 to 16.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Stratified Analysis
Statistical Test of Hypothesis P-Value 0.0164
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.64 to 0.96
Estimation Comments [Not Specified]
3.Primary Outcome
Title Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population
Hide Description Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population
Time Frame Baseline until death (up approximately 53 months)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 350 338
Median (95% Confidence Interval)
Unit of Measure: Months
19.0
(15.7 to 21.5)
14.7
(12.9 to 17.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+Paclitaxel+Carboplatin), Arm C (Bevacizumab+Paclitaxel+Carboplatin)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Stratified Analysis
Statistical Test of Hypothesis P-Value 0.0528
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.842
Confidence Interval (2-Sided) 95%
0.707 to 1.002
Estimation Comments [Not Specified]
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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 356 336
Median (95% Confidence Interval)
Unit of Measure: Months
Teff-high WT Population Number Analyzed 155 participants 129 participants
10.7
(8.4 to 13.0)
7.0
(6.1 to 8.1)
ITT-WT Population Number Analyzed 356 participants 336 participants
8.5
(7.7 to 9.7)
7.0
(6.3 to 8.0)
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.59 to 0.85
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.564
Confidence Interval (2-Sided) 95%
0.418 to 0.760
Estimation Comments [Not Specified]
5.Secondary Outcome
Title PFS, as Determined by the Investigator in Arm B Versus Arm C in Teff High Population and ITT Population
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 400 400
Median (95% Confidence Interval)
Unit of Measure: Months
Teff-high Population Number Analyzed 166 participants 148 participants
11.3
(9.1 to 13.0)
6.8
(5.8 to 7.3)
ITT Population Number Analyzed 400 participants 400 participants
8.3
(7.9 to 9.8)
6.8
(6.0 to 7.1)
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.492
Confidence Interval (2-Sided) 95%
0.374 to 0.649
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.610
Confidence Interval (2-Sided) 95%
0.517 to 0.720
Estimation Comments [Not Specified]
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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 348 356
Median (95% Confidence Interval)
Unit of Measure: Months
Teff-high WT Number Analyzed 161 participants 155 participants
6.3
(5.6 to 7.8)
11.3
(9.1 to 13.0)
ITT-WT Number Analyzed 348 participants 356 participants
6.3
(5.6 to 7.0)
8.3
(7.7 to 9.8)
7.Secondary Outcome
Title PFS, as Determined by the Investigator in Arm B Versus Arm C by PD-L1 Subgroup
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 190 164
Median (95% Confidence Interval)
Unit of Measure: Months
TC2/3 or IC2/3 Subgroup Number Analyzed 129 participants 115 participants
11.1
(8.3 to 13.0)
6.8
(5.8 to 7.7)
TC1/2/3 or IC1/2/3 Subgroup Number Analyzed 190 participants 164 participants
11.0
(8.3 to 12.5)
6.8
(5.8 to 7.3)
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.471
Confidence Interval (2-Sided) 95%
0.352 to 0.647
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.486
Confidence Interval (2-Sided) 95%
0.386 to 0.639
Estimation Comments [Not Specified]
8.Secondary Outcome
Title OS in Arm B Versus Arm C by PD-L1 Subgroup
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 192 165
Median (95% Confidence Interval)
Unit of Measure: Months
TC 2/3 or IC2/3 Population Number Analyzed 129 participants 116 participants
22.2
(17.0 to 26.1)
16.7
(10.5 to 24.2)
TC1/2/3 or IC1/2/3 Population Number Analyzed 192 participants 165 participants
22.5
(18.2 to 26.1)
16.4
(11.2 to 22.9)
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.824
Confidence Interval (2-Sided) 95%
0.580 to 1.169
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.771
Confidence Interval (2-Sided) 95%
0.575 to 1.035
Estimation Comments [Not Specified]
9.Secondary Outcome
Title OS in Arm A Versus Arm C by PD-L1 Subgroup
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 185 165
Median (95% Confidence Interval)
Unit of Measure: Months
TC2/3 or IC2/3 Population Number Analyzed 124 participants 116 participants
26.1
(20.5 to 40.0)
17.0
(10.3 to 22.9)
TC1/2/3 or IC1/2/3 Population Number Analyzed 185 participants 165 participants
24.4
(20.2 to 28.1)
16.0
(11.2 to 20.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.709
Confidence Interval (2-Sided) 95%
0.551 to 0.913
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.662
Confidence Interval (2-Sided) 95%
0.484 to 0.907
Estimation Comments [Not Specified]
10.Secondary Outcome
Title OS in Arm B Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population
Hide Description [Not Specified]
Time Frame Baseline until death (up to approximately 34 months)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 400 400
Median (95% Confidence Interval)
Unit of Measure: Months
Teff High-WT Population Number Analyzed 156 participants 129 participants
25.0 [1] 
(17.8 to NA)
16.7 [1] 
(12.4 to NA)
Teff High Population Number Analyzed 166 participants 148 participants
25.2 [1] 
(19.1 to NA)
16.7 [1] 
(12.4 to NA)
ITT Population Number Analyzed 400 participants 400 participants
19.8
(17.4 to 24.2)
14.9
(13.4 to 17.1)
[1]
Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.831
Confidence Interval (2-Sided) 95%
0.592 to 1.167
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.802
Confidence Interval (2-Sided) 95%
0.579 to 1.113
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.764
Confidence Interval (2-Sided) 95%
0.630 to 0.926
Estimation Comments [Not Specified]
11.Secondary Outcome
Title OS in Arm A Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population
Hide Description [Not Specified]
Time Frame Baseline until death (up approximately 53 months)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 402 400
Median (95% Confidence Interval)
Unit of Measure: Months
Teff-high WT Population Number Analyzed 163 participants 130 participants
21.3
(17.6 to 26.3)
16.3
(11.2 to 22.3)
Teff-high Population Number Analyzed 177 participants 148 participants
21.0
(17.1 to 26.0)
16.7
(11.4 to 21.6)
ITT Population Number Analyzed 402 participants 400 participants
19.0
(16.3 to 21.5)
15.0
(13.4 to 17.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.786
Confidence Interval (2-Sided) 95%
0.595 to 1.038
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.815
Confidence Interval (2-Sided) 95%
0.626 to 1.061
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.861
Confidence Interval (2-Sided) 95%
0.733 to 1.011
Estimation Comments [Not Specified]
12.Secondary Outcome
Title OS in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population
Hide Description [Not Specified]
Time Frame Baseline until death (up approximately 53 months)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 350 359
Median (95% Confidence Interval)
Unit of Measure: Months
Teff High-WT Population Number Analyzed 163 participants 156 participants
21.3
(17.6 to 26.3)
25.8
(19.1 to 32.6)
ITT-WT Population Number Analyzed 350 participants 359 participants
19.0
(15.7 to 21.5)
19.5
(17.0 to 22.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+Paclitaxel+Carboplatin), Arm B (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.901
Confidence Interval (2-Sided) 95%
0.683 to 1.188
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Duration of Response (DOR), as Determined By Investigator in Arm B Versus Arm C
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 224 159
Median (95% Confidence Interval)
Unit of Measure: Months
Teff high-WT Population Number Analyzed 106 participants 68 participants
11.2
(9.7 to 15.7)
5.7
(4.9 to 7.0)
ITT-WT Population Number Analyzed 224 participants 159 participants
9.0
(6.9 to 11.4)
5.7
(5.1 to 6.5)
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.523
Confidence Interval (2-Sided) 95%
0.406 to 0.675
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.420
Confidence Interval (2-Sided) 95%
0.283 to 0.624
Estimation Comments [Not Specified]
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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 347 353 331
Measure Type: Number
Unit of Measure: Percentage
Teff-high WT Population Number Analyzed 161 participants 153 participants 127 participants
54.0 69.3 53.5
ITT-WT Population Number Analyzed 347 participants 353 participants 331 participants
49.3 63.5 48.0
15.Secondary Outcome
Title OS Rates at Years 1 and 2 in Arm B Versus Arm C
Hide 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.
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 235 196
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
1-Year Teff-high WT Population Number Analyzed 105 participants 71 participants
68.63
(61.28 to 75.98)
58.74
(50.03 to 67.45)
1-Year ITT-WT Population Number Analyzed 235 participants 196 participants
67.32
(62.41 to 72.22)
60.63
(55.34 to 65.93)
2-Year Teff-high WT Population Number Analyzed 21 participants 15 participants
52.03
(43.12 to 60.94)
41.70
(31.55 to 51.85)
2-Year ITT-WT Population Number Analyzed 34 participants 29 participants
43.42
(36.94 to 49.90)
33.71
(27.44 to 39.98)
Hide 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 [Not Specified]
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Event Free Rate
Estimated Value 6.68
Confidence Interval (2-Sided) 95%
-0.54 to 13.90
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Event Free Rate
Estimated Value 9.71
Confidence Interval (2-Sided) 95%
0.70 to 18.73
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Event Free Rate
Estimated Value 9.89
Confidence Interval (2-Sided) 95%
-1.51 to 21.29
Estimation Comments [Not Specified]
Hide 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 [Not Specified]
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Event Free Rate
Estimated Value 10.34
Confidence Interval (2-Sided) 95%
-3.17 to 23.84
Estimation Comments [Not Specified]
16.Secondary Outcome
Title OS Rates at Years 1 and 2 in Arm A Versus Arm C
Hide 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.
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 222 197
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
1-Year Teff-high WT Population Number Analyzed 110 participants 72 participants
67.48
(60.29 to 74.68)
56.92
(48.32 to 65.53)
2-Year Teff-high WT Population Number Analyzed 75 participants 49 participants
46.01
(38.36 to 53.66)
38.74
(30.26 to 47.22)
1-Year ITT-WT Population Number Analyzed 222 participants 197 participants
64.06
(59.02 to 69.11)
59.89
(54.61 to 65.17)
2-Year ITT-WT Population Number Analyzed 143 participants 104 participants
41.45
(36.26 to 46.64)
31.79
(26.75 to 36.82)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Event Free Rate
Estimated Value 4.18
Confidence Interval (2-Sided) 95%
-3.13 to 11.48
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Event Free Rate
Estimated Value 9.67
Confidence Interval (2-Sided) 95%
2.43 to 16.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Event Free Rate
Estimated Value 10.56
Confidence Interval (2-Sided) 95%
-0.65 to 21.77
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Event Free Rate
Estimated Value 7.27
Confidence Interval (2-Sided) 95%
-4.15 to 18.69
Estimation Comments [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 348 356 336
Median (95% Confidence Interval)
Unit of Measure: Months
Dyspnea in Teff-high WT Population Number Analyzed 161 participants 155 participants 129 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Dyspnea in ITT-WT Population Number Analyzed 348 participants 356 participants 336 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]

Value is not available due to an insufficient number of participants with the event.

Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.

Hide Statistical Analysis 1
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 0.6899
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.909
Confidence Interval (2-Sided) 95%
0.571 to 1.450
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.671
Confidence Interval (2-Sided) 95%
0.413 to 1.089
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
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 0.1730
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.232
Confidence Interval 95%
0.912 to 1.665
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.084
Confidence Interval (2-Sided) 95%
0.792 to 1.483
Estimation Comments [Not Specified]
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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 348 356 336
Median (95% Confidence Interval)
Unit of Measure: Months
Cough in Teff-high WT Population Number Analyzed 161 participants 155 participants 129 participants
NA [1] 
(NA to NA)
NA [2] 
(21.0 to NA)
NA [1] 
(NA to NA)
Dyspnea in Teff-high WT Population Number Analyzed 161 participants 155 participants 129 participants
NA [2] 
(5.6 to NA)
NA [1] 
(NA to NA)
NA [2] 
(6.3 to NA)
Chest Pain in Teff-high WT Population Number Analyzed 161 participants 155 participants 129 participants
NA [1] 
(NA to NA)
22.2 [3] 
(22.2 to NA)
18.4 [3] 
(18.4 to NA)
Arm and/or Shoulder Pain in Teff-high WT Number Analyzed 161 participants 155 participants 129 participants
NA [2] 
(18.3 to NA)
19.5 [3] 
(12.5 to NA)
NA [2] 
(12.7 to NA)
Cough in ITT-WT Population Number Analyzed 348 participants 356 participants 336 participants
NA [1] 
(NA to NA)
NA [2] 
(21.0 to NA)
NA [1] 
(NA to NA)
Dyspnea in ITT-WT Population Number Analyzed 348 participants 356 participants 336 participants
21.9 [3] 
(9.7 to NA)
NA [1] 
(NA to NA)
NA [2] 
(10.0 to NA)
Arm and/or Shoulder Pain in ITT-WT Number Analyzed 348 participants 356 participants 336 participants
NA [2] 
(18.3 to NA)
19.5 [3] 
(15.2 to NA)
NA [1] 
(NA to NA)
Pain in Chest in ITT-WT Population Number Analyzed 348 participants 356 participants 336 participants
NA [1] 
(NA to NA)
NA [2] 
(22.2 to NA)
NA [2] 
(18.4 to NA)
[1]

Value is not available due to an insufficient number of participants with the event.

Median is not reached and the confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.

[2]

Value is not available due to an insufficient number of participants with the event.

Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.

[3]
Upper confidence limit is not estimable by Brookmeyer and Crowley method due to insufficient observed events.
Hide Statistical Analysis 1
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 0.8816
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.041
Confidence Interval (2-Sided) 95%
0.614 to 1.763
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.741
Confidence Interval (2-Sided) 95%
0.419 to 1.309
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
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 0.7578
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.936
Confidence Interval (2-Sided) 95%
0.616 to 1.422
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.041
Confidence Interval (2-Sided) 95%
0.694 to 1.560
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
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 0.1289
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.659
Confidence Interval (2-Sided) 95%
0.383 to 1.133
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.729
Confidence Interval (2-Sided) 95%
0.430 to 1.235
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
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 0.7163
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.090
Confidence Interval (2-Sided) 95%
0.685 to 1.732
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.693
Confidence Interval (2-Sided) 95%
0.420 to 1.145
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
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 0.9568
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.010
Confidence Interval (2-Sided) 95%
0.713 to 1.430
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.891
Confidence Interval (2-Sided) 95%
0.619 to 1.284
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
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 0.4012
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.893
Confidence Interval (2-Sided) 95%
0.685 to 1.163
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.050
Confidence Interval (2-Sided) 95%
0.809 to 1.363
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
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 0.7126
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.057
Confidence Interval (2-Sided) 95%
0.786 to 1.422
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.921
Confidence Interval (2-Sided) 95%
0.675 to 1.258
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
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 0.3134
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.829
Confidence Interval (2-Sided) 95%
0.576 to 1.194
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Arm A (Atezolizumab+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 [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.910
Confidence Interval (2-Sided) 95%
0.633 to 1.309
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
20.Secondary Outcome
Title Percentage of Participants With Adverse Events
Hide Description [Not Specified]
Time Frame Baseline up to approximately 63 months
Outcome Measure Data Not Reported
21.Secondary Outcome
Title Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Hide Description [Not Specified]
Time Frame Baseline up to approximately 29 months
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 389 376
Measure Type: Number
Unit of Measure: Percentage of Participants
4.6 2.9
22.Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Arm A and Arm B
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 378 364
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Cycle 1 Day 1 Number Analyzed 378 participants 364 participants
410  (157) 414  (127)
Cycle 3 Day 1 Number Analyzed 310 participants 302 participants
498  (160) 540  (198)
23.Secondary Outcome
Title Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Arm A and Arm B
Hide Description [Not Specified]
Time Frame Day 21 of Cycles 1, 2 3, and 7 (Cycle length=21 days)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 354 345
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Cycle 1 Day 21 Number Analyzed 354 participants 345 participants
76.4  (37.7) 80.8  (41.4)
Cycle 2 Day 21 Number Analyzed 322 participants 319 participants
119  (55.7) 130  (57.1)
Cycle 3 Day 21 Number Analyzed 312 participants 307 participants
146  (58.9) 160  (102)
Cycle 7 Day 21 Number Analyzed 230 participants 249 participants
219  (89.6) 220  (99.0)
24.Secondary Outcome
Title Plasma Concentrations for Carboplatin in Arm A, Arm B, and Arm C
Hide Description [Not Specified]
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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 28 35 24
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cy1D1 Pre-dose Number Analyzed 28 participants 35 participants 24 participants
NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Cy1D1 Before End of Infusion Number Analyzed 26 participants 32 participants 24 participants
18300  (9610) 18300  (11900) 17200  (9860)
Cy1D1 After Infusion Number Analyzed 26 participants 31 participants 22 participants
11700  (5570) 13900  (14300) 10100  (5320)
Cy2D21 Number Analyzed 19 participants 27 participants 17 participants
176  (82.9) 190  (113) 143  (73.0)
Cy3D1 Before End of Infusion Number Analyzed 18 participants 28 participants 16 participants
20900  (8330) 18700  (9410) 20600  (12900)
Cy3D1 After Infusion Number Analyzed 20 participants 27 participants 17 participants
11700  (6990) 12200  (7480) 10400  (4150)
[1]
Predose of Cycle 1 Day 1 administration of Carboplatin.
25.Secondary Outcome
Title Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C
Hide Description [Not Specified]
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)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 28 35 24
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cy1D1 Pre-dose Number Analyzed 28 participants 35 participants 24 participants
NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Cy1D1 Before End of Infusion Number Analyzed 26 participants 34 participants 24 participants
4850  (2800) 6440  (3640) 5560  (2590)
Cy1D1 After Infusion Number Analyzed 27 participants 32 participants 23 participants
2300  (2790) 2490  (3020) 1980  (1780)
Cy2D21 Number Analyzed 2 participants 3 participants 0 participants
NA [2]   (NA) NA [2]   (NA)
Cy3D1 Before End Of Infusion Number Analyzed 19 participants 25 participants 16 participants
5810  (3610) 7810  (4510) 7810  (5160)
Cy3D1 After Infusion Number Analyzed 19 participants 27 participants 17 participants
1800  (1660) 2990  (5830) 1930  (1380)
[1]
Predose of Cycle 1 Day 1 administration of Paclitaxel.
[2]
Mean or SD is not reported because more than half of the samples at the specified timepoint are below the limit of quantification.
26.Secondary Outcome
Title Cmax of Bevacizumab in Arm B and Arm C
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length=21 days)
Hide Outcome Measure Data
Hide 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)
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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.
Overall Number of Participants Analyzed 205 215
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Cycle 1 Day 1 Number Analyzed 205 participants 215 participants
329  (129) 323  (95.0)
Cycle 3 Day 1 Number Analyzed 154 participants 168 participants
413  (126) 430  (123)
27.Secondary Outcome
Title Cmin of Bevacizumab in Arm B and Arm C
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 and Cycle 2 Day 21 (Cycle length=21 days)
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 325 348
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Cycle 1 Day 1 Number Analyzed 325 participants 348 participants
NA [1]   (NA) NA [1]   (NA)
Cycle 2 Day 21 Number Analyzed 280 participants 316 participants
98.0  (50.9) 90.4  (36.8)
[1]
Predose of Cycle 1 Day 1 administration of Bevacizumab.
Time Frame From the first study drug to the data cutoff date 13 Sept 2019 (up to approximately 53 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm B Arm A Arm C
Hide Arm/Group Description Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin Atezolizumab+Paclitaxel+Carboplatin Bevacizumab+Paclitaxel+Carboplatin
All-Cause Mortality
Arm B Arm A Arm C
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   272/400 (68.00%)      275/402 (68.41%)      301/400 (75.25%)    
Hide Serious Adverse Events
Arm B Arm A Arm C
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   187/393 (47.58%)      169/400 (42.25%)      142/394 (36.04%)    
Blood and lymphatic system disorders       
ANAEMIA  1  5/393 (1.27%)  5 5/400 (1.25%)  6 4/394 (1.02%)  4
BONE MARROW FAILURE  1  1/393 (0.25%)  1 0/400 (0.00%)  0 1/394 (0.25%)  1
FEBRILE NEUTROPENIA  1  27/393 (6.87%)  30 13/400 (3.25%)  13 17/394 (4.31%)  18
LEUKOPENIA  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
NEUTROPENIA  1  4/393 (1.02%)  4 1/400 (0.25%)  1 2/394 (0.51%)  2
NORMOCHROMIC ANAEMIA  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
PANCYTOPENIA  1  1/393 (0.25%)  1 0/400 (0.00%)  0 3/394 (0.76%)  3
SPONTANEOUS HAEMATOMA  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
THROMBOCYTOPENIA  1  6/393 (1.53%)  6 1/400 (0.25%)  1 2/394 (0.51%)  2
Cardiac disorders       
ACUTE MYOCARDIAL INFARCTION  1  2/393 (0.51%)  2 1/400 (0.25%)  1 3/394 (0.76%)  3
ATRIAL FIBRILLATION  1  2/393 (0.51%)  2 2/400 (0.50%)  2 1/394 (0.25%)  1
ATRIAL FLUTTER  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
ATRIOVENTRICULAR BLOCK SECOND DEGREE  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
CARDIAC ARREST  1  1/393 (0.25%)  1 1/400 (0.25%)  1 0/394 (0.00%)  0
CARDIAC FAILURE  1  2/393 (0.51%)  2 0/400 (0.00%)  0 1/394 (0.25%)  1
CARDIAC FAILURE CONGESTIVE  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
CORONARY ARTERY DISEASE  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
LEFT VENTRICULAR DYSFUNCTION  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
MYOCARDIAL INFARCTION  1  1/393 (0.25%)  3 2/400 (0.50%)  2 1/394 (0.25%)  1
MYOCARDIAL ISCHAEMIA  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
PERICARDIAL EFFUSION  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
PERICARDITIS  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
TACHYARRHYTHMIA  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
VENTRICULAR TACHYCARDIA  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
Endocrine disorders       
ADRENAL INSUFFICIENCY  1  2/393 (0.51%)  2 1/400 (0.25%)  1 1/394 (0.25%)  1
ADRENOCORTICAL INSUFFICIENCY ACUTE  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
DIABETES INSIPIDUS  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
HYPOPHYSITIS  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
HYPOTHYROIDISM  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
SECONDARY ADRENOCORTICAL INSUFFICIENCY  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
Eye disorders       
OPTIC NEUROPATHY  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
Gastrointestinal disorders       
ABDOMINAL PAIN  1  1/393 (0.25%)  1 2/400 (0.50%)  2 3/394 (0.76%)  3
ABDOMINAL PAIN LOWER  1  1/393 (0.25%)  1 1/400 (0.25%)  1 0/394 (0.00%)  0
ABDOMINAL PAIN UPPER  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
COLITIS  1  6/393 (1.53%)  6 1/400 (0.25%)  1 0/394 (0.00%)  0
COLITIS ISCHAEMIC  1  1/393 (0.25%)  1 0/400 (0.00%)  0 2/394 (0.51%)  2
CONSTIPATION  1  1/393 (0.25%)  1 1/400 (0.25%)  1 0/394 (0.00%)  0
DIARRHOEA  1  10/393 (2.54%)  11 8/400 (2.00%)  8 3/394 (0.76%)  3
DIVERTICULAR PERFORATION  1  1/393 (0.25%)  1 1/400 (0.25%)  1 0/394 (0.00%)  0
DUODENAL ULCER  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
DYSPHAGIA  1  1/393 (0.25%)  1 2/400 (0.50%)  3 0/394 (0.00%)  0
FAECALOMA  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
FOOD POISONING  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
GASTRIC HAEMORRHAGE  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
GASTRITIS  1  4/393 (1.02%)  4 0/400 (0.00%)  0 0/394 (0.00%)  0
GASTROINTESTINAL HAEMORRHAGE  1  1/393 (0.25%)  1 2/400 (0.50%)  2 0/394 (0.00%)  0
GLOSSODYNIA  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
ILEUS PARALYTIC  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
INGUINAL HERNIA  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
INTESTINAL ANGINA  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
INTESTINAL HAEMORRHAGE  1  1/393 (0.25%)  2 0/400 (0.00%)  0 0/394 (0.00%)  0
INTESTINAL INFARCTION  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
INTESTINAL ISCHAEMIA  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
INTESTINAL OBSTRUCTION  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
INTESTINAL PERFORATION  1  0/393 (0.00%)  0 0/400 (0.00%)  0 2/394 (0.51%)  2
IRRITABLE BOWEL SYNDROME  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
LARGE INTESTINAL HAEMORRHAGE  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
LARGE INTESTINE PERFORATION  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
NAUSEA  1  7/393 (1.78%)  7 1/400 (0.25%)  1 3/394 (0.76%)  3
OESOPHAGEAL FOOD IMPACTION  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
PANCREATITIS ACUTE  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
VOMITING  1  5/393 (1.27%)  5 4/400 (1.00%)  5 3/394 (0.76%)  3
General disorders       
ASTHENIA  1  0/393 (0.00%)  0 1/400 (0.25%)  1 1/394 (0.25%)  1
CATHETER SITE ERYTHEMA  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
CHEST PAIN  1  4/393 (1.02%)  4 1/400 (0.25%)  2 6/394 (1.52%)  7
COMPLICATION ASSOCIATED WITH DEVICE  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
DEATH  1  2/393 (0.51%)  2 1/400 (0.25%)  1 2/394 (0.51%)  2
GENERAL PHYSICAL HEALTH DETERIORATION  1  2/393 (0.51%)  2 0/400 (0.00%)  0 2/394 (0.51%)  2
INFLUENZA LIKE ILLNESS  1  0/393 (0.00%)  0 1/400 (0.25%)  1 1/394 (0.25%)  1
INFUSION SITE EXTRAVASATION  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
MUCOSAL INFLAMMATION  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
NON-CARDIAC CHEST PAIN  1  1/393 (0.25%)  1 0/400 (0.00%)  0 1/394 (0.25%)  1
OEDEMA PERIPHERAL  1  1/393 (0.25%)  1 0/400 (0.00%)  0 1/394 (0.25%)  1
PAIN  1  1/393 (0.25%)  1 1/400 (0.25%)  1 0/394 (0.00%)  0
PYREXIA  1  7/393 (1.78%)  7 6/400 (1.50%)  6 1/394 (0.25%)  1
Hepatobiliary disorders       
CHOLANGITIS  1  3/393 (0.76%)  3 0/400 (0.00%)  0 1/394 (0.25%)  1
CHOLANGITIS ACUTE  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
CHOLELITHIASIS  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
HEPATITIS  1  2/393 (0.51%)  2 1/400 (0.25%)  1 0/394 (0.00%)  0
HEPATOMEGALY  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
HEPATOTOXICITY  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
Immune system disorders       
ANAPHYLACTIC REACTION  1  0/393 (0.00%)  0 2/400 (0.50%)  2 0/394 (0.00%)  0
DRUG HYPERSENSITIVITY  1  1/393 (0.25%)  2 2/400 (0.50%)  2 0/394 (0.00%)  0
HYPERSENSITIVITY  1  1/393 (0.25%)  2 1/400 (0.25%)  1 2/394 (0.51%)  2
Infections and infestations       
ABDOMINAL SEPSIS  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
ANAL ABSCESS  1  1/393 (0.25%)  1 1/400 (0.25%)  1 1/394 (0.25%)  1
BACTERAEMIA  1  1/393 (0.25%)  1 1/400 (0.25%)  1 0/394 (0.00%)  0
BACTERIAL INFECTION  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
BONE ABSCESS  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
BRONCHITIS  1  3/393 (0.76%)  3 1/400 (0.25%)  1 2/394 (0.51%)  2
BURSITIS INFECTIVE  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
CELLULITIS  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
CHRONIC SINUSITIS  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
CLOSTRIDIUM DIFFICILE INFECTION  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
DEVICE RELATED INFECTION  1  0/393 (0.00%)  0 2/400 (0.50%)  2 0/394 (0.00%)  0
DIVERTICULITIS  1  1/393 (0.25%)  2 1/400 (0.25%)  1 1/394 (0.25%)  1
EMPYEMA  1  0/393 (0.00%)  0 2/400 (0.50%)  2 0/394 (0.00%)  0
ENCEPHALITIS  1  1/393 (0.25%)  1 1/400 (0.25%)  1 0/394 (0.00%)  0
ENDOCARDITIS BACTERIAL  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
ENTERITIS INFECTIOUS  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
ENTEROCOLITIS BACTERIAL  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
FEBRILE INFECTION  1  0/393 (0.00%)  0 1/400 (0.25%)  1 1/394 (0.25%)  1
GASTROENTERITIS  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
GASTROENTERITIS CLOSTRIDIAL  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
HAEMORRHAGIC PNEUMONIA  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
HEPATITIS A  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
HEPATITIS C  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
HERPES ZOSTER  1  0/393 (0.00%)  0 2/400 (0.50%)  2 0/394 (0.00%)  0
INFECTED SKIN ULCER  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
INFECTION  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
INFECTIOUS PLEURAL EFFUSION  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE  1  1/393 (0.25%)  1 1/400 (0.25%)  1 0/394 (0.00%)  0
INFLUENZA  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
KLEBSIELLA SEPSIS  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
LARGE INTESTINE INFECTION  1  2/393 (0.51%)  2 0/400 (0.00%)  0 0/394 (0.00%)  0
LOWER RESPIRATORY TRACT INFECTION  1  1/393 (0.25%)  1 3/400 (0.75%)  4 0/394 (0.00%)  0
LUNG INFECTION  1  2/393 (0.51%)  2 4/400 (1.00%)  4 1/394 (0.25%)  1
NEUTROPENIC SEPSIS  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
OSTEOMYELITIS  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
PARAINFLUENZAE VIRUS INFECTION  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
PAROTITIS  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
PNEUMONIA  1  26/393 (6.62%)  28 17/400 (4.25%)  19 17/394 (4.31%)  18
PNEUMONIA ADENOVIRAL  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
PNEUMONIA BACTERIAL  1  3/393 (0.76%)  3 0/400 (0.00%)  0 0/394 (0.00%)  0
PROSTATIC ABSCESS  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
PYOPNEUMOTHORAX  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
RESPIRATORY SYNCYTIAL VIRUS BRONCHITIS  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
RESPIRATORY SYNCYTIAL VIRUS INFECTION  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
RESPIRATORY TRACT INFECTION  1  4/393 (1.02%)  4 2/400 (0.50%)  2 2/394 (0.51%)  2
RESPIRATORY TRACT INFECTION FUNGAL  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
SALMONELLOSIS  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
SCROTAL ABSCESS  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
SEPSIS  1  3/393 (0.76%)  4 3/400 (0.75%)  3 5/394 (1.27%)  5
SEPTIC SHOCK  1  2/393 (0.51%)  2 2/400 (0.50%)  2 0/394 (0.00%)  0
STAPHYLOCOCCAL BACTERAEMIA  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
STAPHYLOCOCCAL INFECTION  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
TOOTH ABSCESS  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
UPPER RESPIRATORY TRACT INFECTION  1  1/393 (0.25%)  1 1/400 (0.25%)  1 0/394 (0.00%)  0
URINARY TRACT INFECTION  1  3/393 (0.76%)  3 4/400 (1.00%)  4 2/394 (0.51%)  2
VASCULAR DEVICE INFECTION  1  2/393 (0.51%)  2 1/400 (0.25%)  1 0/394 (0.00%)  0
VIRAL INFECTION  1  3/393 (0.76%)  3 0/400 (0.00%)  0 0/394 (0.00%)  0
Injury, poisoning and procedural complications       
ACCIDENTAL OVERDOSE  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
FALL  1  2/393 (0.51%)  2 0/400 (0.00%)  0 0/394 (0.00%)  0
FEMUR FRACTURE  1  1/393 (0.25%)  1 2/400 (0.50%)  2 1/394 (0.25%)  1
FRACTURE  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
HIP FRACTURE  1  1/393 (0.25%)  1 2/400 (0.50%)  2 0/394 (0.00%)  0
HUMERUS FRACTURE  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
INFUSION RELATED REACTION  1  1/393 (0.25%)  1 3/400 (0.75%)  3 0/394 (0.00%)  0
PROCEDURAL COMPLICATION  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
PROCEDURAL PAIN  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
RADIATION OESOPHAGITIS  1  0/393 (0.00%)  0 0/400 (0.00%)  0 0/394 (0.00%)  0
RIB FRACTURE  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
SPINAL COMPRESSION FRACTURE  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
STERNAL FRACTURE  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
WOUND COMPLICATION  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
Investigations       
ALANINE AMINOTRANSFERASE INCREASED  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
ASPARTATE AMINOTRANSFERASE INCREASED  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
BLOOD LACTATE DEHYDROGENASE INCREASED  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
BLOOD PRESSURE INCREASED  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
C-REACTIVE PROTEIN INCREASED  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
GENERAL PHYSICAL CONDITION ABNORMAL  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
HEPATIC ENZYME INCREASED  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
LIPASE INCREASED  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
NEUTROPHIL COUNT DECREASED  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
PLATELET COUNT DECREASED  1  2/393 (0.51%)  2 0/400 (0.00%)  0 2/394 (0.51%)  2
TRANSAMINASES INCREASED  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
TROPONIN INCREASED  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
WEIGHT DECREASED  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
WHITE BLOOD CELL COUNT DECREASED  1  2/393 (0.51%)  2 0/400 (0.00%)  0 1/394 (0.25%)  1
Metabolism and nutrition disorders       
DECREASED APPETITE  1  2/393 (0.51%)  2 0/400 (0.00%)  0 0/394 (0.00%)  0
DEHYDRATION  1  7/393 (1.78%)  9 3/400 (0.75%)  3 6/394 (1.52%)  6
FAILURE TO THRIVE  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
HYPERCALCAEMIA  1  0/393 (0.00%)  0 1/400 (0.25%)  1 0/394 (0.00%)  0
HYPERGLYCAEMIA  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  2
HYPOKALAEMIA  1  2/393 (0.51%)  2 1/400 (0.25%)  1 0/394 (0.00%)  0
HYPONATRAEMIA  1  2/393 (0.51%)  2 1/400 (0.25%)  1 1/394 (0.25%)  1
HYPOPHOSPHATAEMIA  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
Musculoskeletal and connective tissue disorders       
ARTHRALGIA  1  1/393 (0.25%)  1 2/400 (0.50%)  2 1/394 (0.25%)  1
BACK PAIN  1  2/393 (0.51%)  2 1/400 (0.25%)  1 3/394 (0.76%)  3
BONE PAIN  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
COMPARTMENT SYNDROME  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
FLANK PAIN  1  0/393 (0.00%)  0 2/400 (0.50%)  2 0/394 (0.00%)  0
MUSCULAR WEAKNESS  1  1/393 (0.25%)  1 0/400 (0.00%)  0 1/394 (0.25%)  1
MUSCULOSKELETAL CHEST PAIN  1  0/393 (0.00%)  0 0/400 (0.00%)  0 1/394 (0.25%)  1
MUSCULOSKELETAL PAIN  1  1/393 (0.25%)  1 1/400 (0.25%)  1 1/394 (0.25%)  1
MYALGIA  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
OSTEOLYSIS  1  1/393 (0.25%)  1 0/400 (0.00%)  0 0/394 (0.00%)  0
PAIN IN EXTREMITY  1  1/393 (0.25%)  1 1/400 (0.25%)  1 0/394 (0.00%)  0
SOFT TISSUE NECROSIS  1