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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02420821
Recruitment Status : Active, not recruiting
First Posted : April 20, 2015
Results First Posted : October 3, 2018
Last Update Posted : May 28, 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 Renal Cell Carcinoma
Interventions Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Drug: Bevacizumab
Drug: Sunitinib
Enrollment 915
Recruitment Details  
Pre-assignment Details A total of 1228 participants were screened, out of which, 915 participants were enrolled into the study.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description Participants received sunitinib at a dose of 50 milligrams (mg) administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to disease progression (PD) as determined by the investigator, withdrawal of consent, or death, whichever occurred first. Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 milligrams per kilogram (mg/kg) administered via intravenous (IV) infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Period Title: Overall Study
Started 461 454
Completed 293 317
Not Completed 168 137
Reason Not Completed
Lost to Follow-up             2             0
Non-compliance             1             2
Physician Decision             5             2
Withdrawal by Subject             31             17
Death             129             116
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab Total
Hide Arm/Group Description Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first. Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first. Total of all reporting groups
Overall Number of Baseline Participants 461 454 915
Hide Baseline Analysis Population Description
Analysis was performed on the intent-to-treat (ITT) population, which included all randomized participants whether or not the assigned study treatment was received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 461 participants 454 participants 915 participants
59.9  (9.9) 61.6  (10.4) 60.7  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 461 participants 454 participants 915 participants
Female
109
  23.6%
137
  30.2%
246
  26.9%
Male
352
  76.4%
317
  69.8%
669
  73.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 461 participants 454 participants 915 participants
Hispanic or Latino
32
   6.9%
25
   5.5%
57
   6.2%
Not Hispanic or Latino
386
  83.7%
391
  86.1%
777
  84.9%
Unknown or Not Reported
43
   9.3%
38
   8.4%
81
   8.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 461 participants 454 participants 915 participants
American Indian or Alaska Native
1
   0.2%
2
   0.4%
3
   0.3%
Asian
77
  16.7%
94
  20.7%
171
  18.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.2%
1
   0.1%
Black or African American
4
   0.9%
1
   0.2%
5
   0.5%
White
334
  72.5%
326
  71.8%
660
  72.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
45
   9.8%
30
   6.6%
75
   8.2%
1.Primary Outcome
Title Percentage of Participants With Disease Progression as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death From Any Cause in Programmed Death-Ligand 1 (PD-L1)-Selected Population
Hide Description Tumor response was assessed by the investigator according to RECIST v1.1. Disease Progression (PD) was defined as greater than or equal to (>/=) 20 percent (%) relative increase in the sum of diameters (SoD) of all target lesions (TLs), taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 millimeters (mm); >/=1 new lesion(s); and/or unequivocal progression of existing non-TLs.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the PD-L1-Selected Population, which included all participants in the ITT population whose PD-L1 status was immune cell (IC)1/2/3 at the time of randomization.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 184 178
Measure Type: Number
Unit of Measure: percentage of participants
69.6 58.4
2.Primary Outcome
Title Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected Population
Hide Description PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% confidence interval (CI) was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the PD-L1-Selected Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 184 178
Median (95% Confidence Interval)
Unit of Measure: months
7.5
(6.8 to 9.7)
11.2
(8.6 to 14.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0205
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.57 to 0.95
Estimation Comments Hazard ratio was estimated by Cox regression.
3.Primary Outcome
Title Percentage of Participants Who Died of Any Cause in ITT Population
Hide Description Percentage of participants who died of any cause was reported.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 461 454
Measure Type: Number
Unit of Measure: percentage of participants
30.6 27.1
4.Primary Outcome
Title Overall Survival (OS) in ITT Population
Hide Description OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 461 454
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(23.3 to NA)
NA [2] 
(NA to NA)
[1]
Median and upper limit of 95% CI could not be estimated due to high number of censored participants.
[2]
Median and corresponding 95% CI could not be estimated due to high number of censored participants.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0895
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.63 to 1.03
Estimation Comments Hazard ratio was estimated by Cox regression.
5.Secondary Outcome
Title Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population
Hide Description Percentage of participants who died of any cause was reported.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the PD-L1-Selected Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 184 178
Measure Type: Number
Unit of Measure: percentage of participants
34.8 25.3
6.Secondary Outcome
Title OS in PD-L1-Selected Population
Hide Description OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the PD-L1-Selected Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 184 178
Median (95% Confidence Interval)
Unit of Measure: months
23.3 [1] 
(21.3 to NA)
NA [2] 
(NA to NA)
[1]
Upper limit of 95% CI could not be estimated due to high number of censored participants.
[2]
Median and corresponding 95% CI could not be estimated due to high number of censored participants.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0470
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.46 to 1.00
Estimation Comments Hazard ratio was estimated by Cox regression.
7.Secondary Outcome
Title Percentage of Participants With PD as Determined by an Independent Review Committee (IRC) According to RECIST v1.1 or Death From Any Cause in ITT Population
Hide Description Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 461 454
Measure Type: Number
Unit of Measure: percentage of participants
63.6 60.4
8.Secondary Outcome
Title PFS as Determined by an IRC According to RECIST v1.1 in ITT Population
Hide Description PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 461 454
Median (95% Confidence Interval)
Unit of Measure: months
8.3
(7.0 to 9.7)
9.6
(8.3 to 11.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1218
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.74 to 1.04
Estimation Comments Hazard ratio was estimated by Cox regression.
9.Secondary Outcome
Title Percentage of Participants With PD as Determined by an IRC According to RECIST v1.1 or Death From Any Cause in PD-L1-Selected Population
Hide Description Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the PD-L1-Selected Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 184 178
Measure Type: Number
Unit of Measure: percentage of participants
64.7 62.9
10.Secondary Outcome
Title PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected Population
Hide Description PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the PD-L1-Selected Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 184 178
Median (95% Confidence Interval)
Unit of Measure: months
7.2
(6.1 to 11.1)
8.9
(6.9 to 12.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6138
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.72 to 1.21
Estimation Comments Hazard ratio was estimated by Cox regression.
11.Secondary Outcome
Title Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator According to RECIST v1.1 in Objective Response Rate (ORR)-Evaluable Population
Hide Description Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to less than (<) 10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ORR-Evaluable Population, which included all participants in the ITT population with measurable disease at baseline, as determined by the investigator.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 460 454
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.3
(28.97 to 37.77)
36.6
(32.12 to 41.18)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2733
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 3.30
Confidence Interval (2-Sided) 95%
-3.09 to 9.70
Estimation Comments 95% CI for difference in response rates was constructed using Wald method.
12.Secondary Outcome
Title Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable Population
Hide Description DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on DOR-Evaluable Population, which included all participants with a CR/PR in the ORR-Evaluable Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 153 166
Median (95% Confidence Interval)
Unit of Measure: months
14.2 [1] 
(11.3 to NA)
16.6 [1] 
(15.4 to NA)
[1]
Upper limit of 95% CI could not be estimated due to high number of censored participants.
13.Secondary Outcome
Title Percentage of Participants With an Objective Response of CR or PR as Determined by an IRC According to RECIST v1.1 in ORR-Evaluable Population
Hide Description Tumor response was assessed by an IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ORR-Evaluable Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 460 454
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
31.3
(27.09 to 35.76)
33.3
(28.94 to 37.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5121
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 1.96
Confidence Interval (2-Sided) 95%
-4.32 to 8.24
Estimation Comments 95% CI for difference in response rates was constructed using Wald method.
14.Secondary Outcome
Title DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable Population
Hide Description DOR was defined as the time from the first occurrence of CR/PR to PD as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the DOR-Evaluable Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 144 151
Median (95% Confidence Interval)
Unit of Measure: months
18.6 [1] 
(13.8 to NA)
NA [2] 
(16.8 to NA)
[1]
Upper limit of 95% CI could not be estimated due to high number of censored participants.
[2]
Median and Upper limit of 95% CI could not be estimated due to high number of censored participants.
15.Secondary Outcome
Title Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT Population
Hide Description Tumor response was assessed by the investigator according to immune-modified RECIST. PD was defined as >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 461 454
Measure Type: Number
Unit of Measure: percentage of participants
58.1 55.1
16.Secondary Outcome
Title PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT Population
Hide Description PFS was defined as the time from randomization to PD, as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 461 454
Median (95% Confidence Interval)
Unit of Measure: months
12.3
(9.8 to 13.7)
13.9
(12.5 to 15.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0606
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.71 to 1.01
Estimation Comments Hazard ratio was estimated by Cox regression.
17.Secondary Outcome
Title Percentage of Participants With an Objective Response of CR or PR as Determined by the Investigator According to Immune-Modified RECIST in ORR-Evaluable Population
Hide Description Tumor response was assessed by the investigator according to immune-modified RECIST. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ORR-Evaluable Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 460 454
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
35.0
(30.64 to 39.55)
40.1
(35.55 to 44.76)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1011
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value 5.09
Confidence Interval (2-Sided) 95%
-1.40 to 11.58
Estimation Comments 95% CI for difference in response rates was constructed using Wald method.
18.Secondary Outcome
Title DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable Population
Hide Description DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.
Time Frame Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on DOR-Evaluable Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 161 182
Median (95% Confidence Interval)
Unit of Measure: months
19.4
(13.1 to 20.0)
19.4 [1] 
(16.5 to NA)
[1]
Upper limit of 95% CI could not be estimated due to high number of censored participants.
19.Secondary Outcome
Title Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT Population
Hide Description Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 461 454
Measure Type: Number
Unit of Measure: percentage of participants
63.8 60.1
20.Secondary Outcome
Title PFS as Determined by the Investigator According to RECIST v1.1 in ITT Population
Hide Description PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 461 454
Median (95% Confidence Interval)
Unit of Measure: months
8.4
(7.5 to 9.7)
11.2
(9.6 to 13.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0254
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.70 to 0.98
Estimation Comments Hazard ratio was estimated by Cox regression.
21.Secondary Outcome
Title Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in Participants With Sarcomatoid Histology
Hide Description Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population participants with sarcomatoid histology (defined by investigator-assessed conventional histopathology).
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 74 68
Measure Type: Number
Unit of Measure: percentage of participants
85.1 67.6
22.Secondary Outcome
Title PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid Histology
Hide Description PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population participants with sarcomatoid histology.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 74 68
Median (95% Confidence Interval)
Unit of Measure: months
5.3
(3.3 to 6.7)
8.3
(5.4 to 12.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.34 to 0.79
Estimation Comments Hazard ratio was estimated by Cox regression.
23.Secondary Outcome
Title Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid Histology
Hide Description Percentage of participants who died of any cause was reported.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population participants with sarcomatoid histology.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 74 68
Measure Type: Number
Unit of Measure: percentage of participants
50.0 38.2
24.Secondary Outcome
Title OS in Participants With Sarcomatoid Histology
Hide Description OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time Frame Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT Population participants with sarcomatoid histology.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 74 68
Median (95% Confidence Interval)
Unit of Measure: months
15.0 [1] 
(8.7 to NA)
NA [2] 
(18.3 to NA)
[1]
Upper limit of 95% CI could not be estimated due to high number of censored participants.
[2]
Median/upper limit of 95% CI could not be estimated due to high number of censored participants.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Stratified Analysis: Strata were presence of liver metastases, Motzer score, PD-L1 level per interactive voice/web response system (IxRS).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0323
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.56
Confidence Interval (2-Sided) 95%
0.32 to 0.96
Estimation Comments Hazard ratio was estimated by Cox regression.
25.Secondary Outcome
Title Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II Score
Hide Description The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part II, participants were asked to rate how much the symptoms have interfered with 6 areas of function (general activity, walking, work, mood, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely) and total Part II score was calculated as an average of 6-item scores. Repeated measures model-estimated least-squares (LS) mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement. Here, 'Number Analyzed' = number of participants evaluable at specified time point.
Time Frame Baseline (Day 1 Cycle 1); Day 22 Cycle 1; Day 1 and 22 of every cycle from Cycle 2 up to Cycle 19; Cycle length = 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the patient-reported outcome (PRO)-Evaluable Population, which included all participants with a non-missing baseline PRO assessment and >/=1 post-baseline PRO assessment.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 359 373
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Change at Cycle1 Day 22 Number Analyzed 260 participants 301 participants
1.28  (0.13) 0.54  (0.13)
Change at Cycle 2 Day 1 Number Analyzed 276 participants 305 participants
0.76  (0.13) 0.56  (0.13)
Change at Cycle 2 Day 22 Number Analyzed 248 participants 284 participants
1.58  (0.13) 0.56  (0.13)
Change at Cycle 3 Day 1 Number Analyzed 253 participants 297 participants
1.05  (0.13) 0.53  (0.13)
Change at Cycle 3 Day 22 Number Analyzed 226 participants 279 participants
1.63  (0.14) 0.61  (0.13)
Change at Cycle 4 Day 1 Number Analyzed 230 participants 266 participants
1.02  (0.14) 0.59  (0.13)
Change at Cycle 4 Day 22 Number Analyzed 217 participants 252 participants
1.55  (0.14) 0.57  (0.14)
Change at Cycle 5 Day 1 Number Analyzed 211 participants 238 participants
1.18  (0.15) 0.72  (0.14)
Change at Cycle 5 Day 22 Number Analyzed 196 participants 238 participants
1.56  (0.15) 0.78  (0.14)
Change at Cycle 6 Day 1 Number Analyzed 198 participants 224 participants
1.03  (0.15) 0.82  (0.14)
Change at Cycle 6 Day 22 Number Analyzed 183 participants 207 participants
1.44  (0.15) 0.80  (0.15)
Change at Cycle 7 Day 1 Number Analyzed 173 participants 200 participants
1.15  (0.16) 0.72  (0.15)
Change at Cycle 7 Day 22 Number Analyzed 163 participants 191 participants
1.43  (0.16) 0.66  (0.15)
Change at Cycle 8 Day 1 Number Analyzed 161 participants 192 participants
1.06  (0.16) 0.76  (0.15)
Change at Cycle 8 Day 22 Number Analyzed 150 participants 186 participants
1.34  (0.17) 0.69  (0.15)
Change at Cycle 9 Day 1 Number Analyzed 146 participants 185 participants
1.05  (0.17) 0.67  (0.16)
Change at Cycle 9 Day 22 Number Analyzed 135 participants 172 participants
1.46  (0.18) 0.56  (0.16)
Change at Cycle 10 Day 1 Number Analyzed 131 participants 169 participants
1.24  (0.18) 0.61  (0.16)
Change at Cycle 10 Day 22 Number Analyzed 78 participants 151 participants
1.61  (0.20) 0.60  (0.17)
Change at Cycle 11 Day 1 Number Analyzed 100 participants 134 participants
1.12  (0.19) 0.62  (0.17)
Change at Cycle 11 Day 22 Number Analyzed 59 participants 122 participants
1.45  (0.21) 0.61  (0.18)
Change at Cycle 12 Day 1 Number Analyzed 73 participants 110 participants
1.02  (0.21) 0.53  (0.18)
Change at Cycle 12 Day 22 Number Analyzed 47 participants 93 participants
1.45  (0.24) 0.69  (0.20)
Change at Cycle 13 Day 1 Number Analyzed 52 participants 81 participants
0.79  (0.24) 0.80  (0.21)
Change at Cycle 13 Day 22 Number Analyzed 36 participants 72 participants
1.09  (0.27) 0.73  (0.22)
Change at Cycle 14 Day 1 Number Analyzed 39 participants 57 participants
0.86  (0.27) 0.73  (0.24)
Change at Cycle 14 Day 22 Number Analyzed 27 participants 54 participants
1.22  (0.31) 0.83  (0.25)
Change at Cycle 15 Day 1 Number Analyzed 31 participants 43 participants
0.93  (0.31) 0.78  (0.27)
Change at Cycle 15 Day 22 Number Analyzed 17 participants 36 participants
1.67  (0.37) 0.88  (0.29)
Change at Cycle 16 Day 1 Number Analyzed 20 participants 27 participants
0.90  (0.38) 0.98  (0.32)
Change at Cycle 16 Day 22 Number Analyzed 13 participants 22 participants
1.30  (0.43) 1.32  (0.36)
Change at Cycle 17 Day 1 Number Analyzed 13 participants 19 participants
0.80  (0.46) 1.18  (0.40)
Change at Cycle 17 Day 22 Number Analyzed 9 participants 11 participants
0.92  (0.53) 0.95  (0.47)
Change at Cycle 18 Day 1 Number Analyzed 6 participants 9 participants
0.75  (0.64) 0.75  (0.53)
Change at Cycle 18 Day 22 Number Analyzed 3 participants 6 participants
0.65  (0.86) 0.87  (0.63)
Change at Cycle 19 Day 1 Number Analyzed 1 participants 5 participants
0.29  (1.58) 0.80  (0.73)
Change at Cycle 19 Day 22 Number Analyzed 0 participants 2 participants
0.88  (1.03)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 1 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.74
Confidence Interval (2-Sided) 95%
-1.06 to -0.43
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 2 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2085
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.51 to 0.11
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 2 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.02
Confidence Interval (2-Sided) 95%
-1.33 to -0.71
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 3 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-0.82 to -0.20
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 3 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.02
Confidence Interval (2-Sided) 95%
-1.34 to -0.70
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 4 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0098
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.43
Confidence Interval (2-Sided) 95%
-0.76 to -0.10
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 4 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.98
Confidence Interval (2-Sided) 95%
-1.32 to -0.65
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 5 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0080
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-0.80 to -0.12
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 5 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.78
Confidence Interval (2-Sided) 95%
-1.13 to -0.44
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 6 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2512
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.56 to 0.15
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 6 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.65
Confidence Interval (2-Sided) 95%
-1.01 to -0.28
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 7 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0247
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.43
Confidence Interval (2-Sided) 95%
-0.80 to -0.05
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 7 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.77
Confidence Interval (2-Sided) 95%
-1.15 to -0.39
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 8 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1411
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.68 to 0.10
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 8 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.65
Confidence Interval (2-Sided) 95%
-1.05 to -0.25
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 9 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0728
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.78 to 0.03
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 9 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.90
Confidence Interval (2-Sided) 95%
-1.32 to -0.49
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 10 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0041
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.62
Confidence Interval (2-Sided) 95%
-1.05 to -0.20
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 10 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.00
Confidence Interval (2-Sided) 95%
-1.46 to -0.55
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 11 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0353
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-0.96 to -0.03
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 11 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.85
Confidence Interval (2-Sided) 95%
-1.35 to -0.34
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 12 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0582
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-1.01 to 0.02
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 12 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0089
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.76
Confidence Interval (2-Sided) 95%
-1.32 to -0.19
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 13 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9575
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.57 to 0.61
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 13 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2745
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-1.01 to 0.29
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 14 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7088
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.81 to 0.55
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 14 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3077
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-1.13 to 0.36
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 15 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7112
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.93 to 0.63
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 15 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0837
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.79
Confidence Interval (2-Sided) 95%
-1.69 to 0.11
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 16 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8655
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.88 to 1.04
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 16 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9725
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-1.07 to 1.11
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 17 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5285
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
-0.80 to 1.55
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 17 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9663
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-1.34 to 1.40
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 18 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9914
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-1.61 to 1.63
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 18 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8345
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
-1.85 to 2.30
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 19 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7725
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-2.90 to 3.91
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
26.Secondary Outcome
Title Change From Baseline in Symptom Severity as Determined by MDASI Part I Score
Hide Description The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part I, participants were asked to rate how severe the symptoms (pain, fatigue, nausea, disturbed sleep, feeling of being distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, feeling sad, vomiting, numbness or tingling, rash/skin changes, headache, mouth/throat sores, and diarrhea) were when "at their worst" in the last 24 hours. Each item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Mixed-effects model-estimated LS mean score for change from baseline at the end-of treatment is reported for each item, where a negative value indicates improvement.
Time Frame Baseline; End of Treatment (EoT) visit (up to approximately 27 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the PRO-Evaluable Population. Here, 'Overall Number of Participants Analyzed’ = number of participants evaluable for this outcome measure.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 337 358
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Pain: Change at EoT 1.41  (0.15) 0.92  (0.15)
Fatigue: Change at EoT 1.83  (0.15) 1.20  (0.15)
Nausea: Change at EoT 1.20  (0.11) 0.29  (0.11)
Disturbed sleep: Change at EoT 0.71  (0.14) 0.19  (0.14)
Feelings of being distressed: Change at EoT 0.82  (0.14) 0.25  (0.14)
Shortness of breath: Change at EoT 1.15  (0.13) 0.58  (0.13)
Remembering things: Change at EoT 0.93  (0.12) 0.60  (0.11)
Lack of appetite: Change at EoT 1.59  (0.14) 0.40  (0.14)
Drowsy: Change at EoT 1.32  (0.14) 0.79  (0.14)
Dry mouth: Change at EoT 1.67  (0.15) 0.67  (0.15)
Feeling sad: Change at EoT 0.88  (0.14) 0.28  (0.14)
Vomiting: Change at EoT 0.66  (0.09) 0.08  (0.09)
Numbness or tingling: Change at EoT 1.01  (0.12) 0.67  (0.12)
Rash/skin changes: Change at EoT 2.08  (0.13) 1.00  (0.13)
Headache: Change at EoT 0.70  (0.11) 0.66  (0.11)
Mouth/throat sores: Change at EoT 1.76  (0.13) 0.74  (0.13)
Diarrhea: Change at EoT 1.37  (0.10) 0.29  (0.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Pain: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.49
Confidence Interval (2-Sided) 95%
-0.77 to -0.20
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Fatigue: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-0.91 to -0.34
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Nausea: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.91
Confidence Interval (2-Sided) 95%
-1.13 to -0.69
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Disturbed sleep: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-0.79 to -0.25
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Feelings of being distressed: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.56
Confidence Interval (2-Sided) 95%
-0.84 to -0.29
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Shortness of breath: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.56
Confidence Interval (2-Sided) 95%
-0.81 to -0.32
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Remembering things: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0036
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.56 to -0.11
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Lack of appetite: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.19
Confidence Interval (2-Sided) 95%
-1.46 to -0.91
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Drowsy: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-0.81 to -0.27
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Dry mouth: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.00
Confidence Interval (2-Sided) 95%
-1.28 to -0.71
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Feeling sad: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.60
Confidence Interval (2-Sided) 95%
-0.87 to -0.33
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Vomiting: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-0.75 to -0.41
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Numbness or tingling: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0051
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.58 to -0.10
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Rash/Skin Changes: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.08
Confidence Interval (2-Sided) 95%
-1.33 to -0.83
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Headache: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6541
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.26 to 0.16
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Mouth/Throat Sores: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.02
Confidence Interval (2-Sided) 95%
-1.28 to -0.76
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Diarrhea: Mixed-effects model, assuming unstructured covariance matrix, with a term for treatment group, a term for visit time as a continuous variable, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model. The random effects are intercept and slope of visit time.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.07
Confidence Interval (2-Sided) 95%
-1.27 to -0.88
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
27.Secondary Outcome
Title Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale Score
Hide Description The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI interference subscale (6 items) assessed the impact of fatigue on global domains (general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely). Change from baseline in the mean score of all 6 items at each timepoint is reported, where a negative value indicates improvement.
Time Frame Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the PRO-Evaluable Population. Here, 'Overall Number of Participants Analyzed’ = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 368 381
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 368 participants 381 participants
2.11  (2.23) 2.08  (2.38)
Change at Cycle 1 Day 8 Number Analyzed 352 participants 356 participants
0.30  (1.88) 0.37  (1.76)
Change at Cycle 1 Day 15 Number Analyzed 339 participants 352 participants
1.26  (2.49) 1.06  (2.42)
Change at Cycle 1 Day 22 Number Analyzed 258 participants 298 participants
1.34  (2.44) 0.57  (2.04)
Change at Cycle 1 Day 29 Number Analyzed 329 participants 348 participants
1.48  (2.63) 0.66  (2.28)
Change at Cycle 1 Day 36 Number Analyzed 311 participants 344 participants
0.95  (2.29) 0.74  (2.20)
Change at Cycle 2 Day 1 Number Analyzed 271 participants 293 participants
0.38  (2.03) 0.43  (2.09)
Change at Cycle 2 Day 8 Number Analyzed 307 participants 336 participants
0.63  (2.17) 0.68  (2.33)
Change at Cycle 2 Day 15 Number Analyzed 310 participants 319 participants
1.10  (2.35) 0.55  (2.29)
Change at Cycle 2 Day 22 Number Analyzed 245 participants 277 participants
1.24  (2.65) 0.26  (2.14)
Change at Cycle 2 Day 29 Number Analyzed 302 participants 303 participants
1.45  (2.61) 0.51  (2.14)
Change at Cycle 2 Day 36 Number Analyzed 291 participants 311 participants
1.11  (2.46) 0.43  (2.17)
Change at Cycle 3 Day 1 Number Analyzed 238 participants 278 participants
0.76  (2.27) 0.21  (2.12)
Change at Cycle 3 Day 22 Number Analyzed 229 participants 279 participants
1.43  (2.41) 0.36  (2.20)
Change at Cycle 4 Day 1 Number Analyzed 231 participants 266 participants
0.76  (2.27) 0.38  (2.16)
Change at Cycle 4 Day 22 Number Analyzed 219 participants 252 participants
1.47  (2.60) 0.44  (2.33)
Change at Cycle 5 Day 1 Number Analyzed 212 participants 239 participants
1.01  (2.46) 0.52  (2.31)
Change at Cycle 5 Day 22 Number Analyzed 197 participants 238 participants
1.38  (2.22) 0.61  (2.27)
Change at Cycle 6 Day 1 Number Analyzed 199 participants 224 participants
0.88  (2.24) 0.59  (2.15)
Change at Cycle 6 Day 22 Number Analyzed 184 participants 207 participants
1.25  (2.42) 0.52  (2.22)
Change at Cycle 7 Day 1 Number Analyzed 174 participants 200 participants
0.82  (2.35) 0.61  (2.17)
Change at Cycle 7 Day 22 Number Analyzed 164 participants 191 participants
1.05  (2.31) 0.47  (2.16)
Change at Cycle 8 Day 1 Number Analyzed 162 participants 192 participants
0.87  (2.21) 0.63  (2.36)
Change at Cycle 8 Day 22 Number Analyzed 151 participants 186 participants
1.22  (2.21) 0.52  (2.05)
Change at Cycle 9 Day 1 Number Analyzed 147 participants 185 participants
0.93  (2.25) 0.57  (2.27)
Change at Cycle 9 Day 22 Number Analyzed 136 participants 172 participants
1.35  (2.37) 0.37  (2.15)
Change at Cycle 10 Day 1 Number Analyzed 132 participants 169 participants
1.09  (2.53) 0.56  (1.96)
Change at Cycle 10 Day 22 Number Analyzed 78 participants 151 participants
1.62  (2.75) 0.52  (1.95)
Change at Cycle 11 Day 1 Number Analyzed 101 participants 134 participants
0.95  (2.29) 0.60  (1.92)
Change at Cycle 11 Day 22 Number Analyzed 59 participants 122 participants
0.88  (2.57) 0.57  (1.78)
Change at Cycle 12 Day 1 Number Analyzed 73 participants 111 participants
0.89  (2.45) 0.35  (1.75)
Change at Cycle 12 Day 22 Number Analyzed 47 participants 93 participants
0.97  (2.46) 0.58  (1.96)
Change at Cycle 13 Day 1 Number Analyzed 52 participants 81 participants
0.84  (2.29) 0.36  (1.88)
Change at Cycle 13 Day 22 Number Analyzed 36 participants 72 participants
0.76  (2.70) 0.56  (2.06)
Change at Cycle 14 Day 1 Number Analyzed 39 participants 57 participants
0.80  (2.33) 0.73  (1.80)
Change at Cycle 14 Day 22 Number Analyzed 27 participants 54 participants
0.69  (2.73) 0.94  (1.96)
Change at Cycle 15 Day 1 Number Analyzed 31 participants 43 participants
0.95  (2.42) 0.61  (1.41)
Change at Cycle 15 Day 22 Number Analyzed 17 participants 36 participants
1.05  (3.22) 0.91  (1.28)
Change at Cycle 16 Day 1 Number Analyzed 20 participants 27 participants
0.13  (1.49) 1.02  (1.69)
Change at Cycle 16 Day 22 Number Analyzed 13 participants 22 participants
1.05  (1.83) 1.55  (1.96)
Change at Cycle 17 Day 1 Number Analyzed 13 participants 19 participants
0.53  (1.41) 1.25  (1.97)
Change at Cycle 17 Day 22 Number Analyzed 9 participants 11 participants
1.43  (2.16) 0.41  (1.48)
Change at Cycle 18 Day 1 Number Analyzed 7 participants 9 participants
0.79  (1.34) 0.35  (1.46)
Change at Cycle 18 Day 22 Number Analyzed 3 participants 6 participants
1.28  (2.21) 0.17  (1.15)
Change at Cycle 19 Day 1 Number Analyzed 1 participants 5 participants
0.00 -0.80  (0.84)
Change at Cycle 19 Day 22 Number Analyzed 0 participants 2 participants
-0.25  (0.82)
Change at 6 weeks after EoT Number Analyzed 70 participants 42 participants
2.31  (2.52) 1.83  (2.52)
Change at 12 weeks after EoT Number Analyzed 59 participants 36 participants
1.71  (2.66) 1.97  (2.63)
Change at 24 weeks after EoT Number Analyzed 31 participants 25 participants
2.38  (3.11) 2.15  (3.30)
Change at 36 weeks after EoT Number Analyzed 14 participants 18 participants
2.40  (3.32) 1.15  (2.72)
Change at EoT Number Analyzed 168 participants 127 participants
1.57  (2.80) 1.62  (2.98)
Change Within 30 Days of PD Number Analyzed 194 participants 184 participants
1.74  (2.64) 0.74  (2.35)
28.Secondary Outcome
Title Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue Item
Hide Description The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI worst fatigue item assessed the severity of fatigue at its worst in the last 24 hours. The item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Change from baseline in the score at each time point is reported, where a negative value indicates improvement.
Time Frame Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the PRO-Evaluable Population. Here, 'Overall Number of Participants Analyzed’ = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 368 381
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 368 participants 381 participants
3.08  (2.66) 2.98  (2.69)
Change at Cycle 1 Day 8 Number Analyzed 352 participants 356 participants
0.34  (2.35) 0.50  (2.29)
Change at Cycle 1 Day 15 Number Analyzed 339 participants 352 participants
1.32  (2.82) 1.26  (2.92)
Change at Cycle 1 Day 22 Number Analyzed 258 participants 298 participants
1.52  (2.86) 0.49  (2.30)
Change at Cycle 1 Day 29 Number Analyzed 329 participants 348 participants
1.55  (2.99) 0.88  (2.62)
Change at Cycle 1 Day 36 Number Analyzed 311 participants 344 participants
0.77  (2.82) 0.86  (2.50)
Change at Cycle 2 Day 1 Number Analyzed 271 participants 293 participants
0.40  (2.50) 0.45  (2.52)
Change at Cycle 2 Day 8 Number Analyzed 307 participants 336 participants
0.56  (2.68) 0.87  (2.82)
Change at Cycle 2 Day 15 Number Analyzed 310 participants 319 participants
1.09  (2.82) 0.71  (2.78)
Change at Cycle 2 Day 22 Number Analyzed 245 participants 277 participants
1.42  (3.01) 0.31  (2.53)
Change at Cycle 2 Day 29 Number Analyzed 302 participants 303 participants
1.43  (3.08) 0.62  (2.66)
Change at Cycle 2 Day 36 Number Analyzed 291 participants 311 participants
1.09  (3.01) 0.48  (2.76)
Change at Cycle 3 Day 1 Number Analyzed 238 participants 278 participants
0.42  (2.68) 0.40  (2.57)
Change at Cycle 3 Day 22 Number Analyzed 229 participants 279 participants
1.57  (2.98) 0.57  (2.64)
Change at Cycle 4 Day 1 Number Analyzed 231 participants 266 participants
0.64  (2.76) 0.54  (2.49)
Change at Cycle 4 Day 22 Number Analyzed 219 participants 252 participants
1.46  (3.14) 0.58  (2.74)
Change at Cycle 5 Day 1 Number Analyzed 212 participants 239 participants
0.81  (2.75) 0.62  (2.79)
Change at Cycle 5 Day 22 Number Analyzed 197 participants 238 participants
1.60  (2.87) 0.69  (2.83)
Change at Cycle 6 Day 1 Number Analyzed 199 participants 224 participants
0.90  (2.78) 0.86  (2.73)
Change at Cycle 6 Day 22 Number Analyzed 184 participants 207 participants
1.35  (2.79) 0.53  (2.66)
Change at Cycle 7 Day 1 Number Analyzed 174 participants 200 participants
0.79  (2.78) 0.79  (2.70)
Change at Cycle 7 Day 22 Number Analyzed 164 participants 191 participants
1.22  (2.85) 0.65  (2.56)
Change at Cycle 8 Day 1 Number Analyzed 162 participants 192 participants
0.79  (2.69) 0.75  (2.84)
Change at Cycle 8 Day 22 Number Analyzed 151 participants 186 participants
1.40  (2.64) 0.78  (2.67)
Change at Cycle 9 Day 1 Number Analyzed 147 participants 185 participants
0.97  (2.54) 0.61  (2.62)
Change at Cycle 9 Day 22 Number Analyzed 136 participants 172 participants
1.54  (2.92) 0.57  (2.55)
Change at Cycle 10 Day 1 Number Analyzed 132 participants 169 participants
0.95  (2.73) 0.69  (2.46)
Change at Cycle 10 Day 22 Number Analyzed 78 participants 151 participants
1.74  (3.09) 0.63  (2.48)
Change at Cycle 11 Day 1 Number Analyzed 101 participants 134 participants
0.73  (2.80) 0.74  (2.69)
Change at Cycle 11 Day 22 Number Analyzed 59 participants 122 participants
1.15  (3.18) 0.74  (2.52)
Change at Cycle 12 Day 1 Number Analyzed 73 participants 111 participants
0.78  (2.79) 0.61  (2.29)
Change at Cycle 12 Day 22 Number Analyzed 47 participants 93 participants
1.32  (2.89) 0.74  (2.69)
Change at Cycle 13 Day 1 Number Analyzed 52 participants 81 participants
0.35  (2.54) 0.49  (2.46)
Change at Cycle 13 Day 22 Number Analyzed 36 participants 72 participants
0.72  (3.48) 0.65  (2.70)
Change at Cycle 14 Day 1 Number Analyzed 39 participants 57 participants
0.56  (2.84) 0.81  (2.60)
Change at Cycle 14 Day 22 Number Analyzed 27 participants 54 participants
0.37  (3.01) 1.04  (2.40)
Change at Cycle 15 Day 1 Number Analyzed 31 participants 43 participants
0.52  (3.15) 0.93  (2.25)
Change at Cycle 15 Day 22 Number Analyzed 17 participants 36 participants
0.59  (4.08) 0.97  (1.84)
Change at Cycle 16 Day 1 Number Analyzed 20 participants 27 participants
-0.05  (2.61) 1.33  (1.92)
Change at Cycle 16 Day 22 Number Analyzed 13 participants 22 participants
0.77  (3.70) 1.68  (2.10)
Change at Cycle 17 Day 1 Number Analyzed 13 participants 19 participants
-0.62  (3.75) 1.68  (1.97)
Change at Cycle 17 Day 22 Number Analyzed 9 participants 11 participants
1.44  (3.91) 1.18  (1.99)
Change at Cycle 18 Day 1 Number Analyzed 7 participants 9 participants
0.00  (2.00) 1.33  (1.58)
Change at Cycle 18 Day 22 Number Analyzed 3 participants 6 participants
1.00  (1.73) 1.00  (2.10)
Change at Cycle 19 Day 1 Number Analyzed 1 participants 5 participants
-4.00 0.60  (1.34)
Change at Cycle 19 Day 22 Number Analyzed 0 participants 2 participants
0.00  (0.00)
Change at 6 weeks after EoT Number Analyzed 70 participants 42 participants
2.43  (3.25) 2.40  (2.89)
Change at 12 weeks after EoT Number Analyzed 59 participants 36 participants
1.56  (3.41) 2.06  (3.14)
Change at 24 weeks after EoT Number Analyzed 31 participants 25 participants
1.58  (3.82) 1.92  (3.46)
Change at 36 weeks after EoT Number Analyzed 14 participants 18 participants
1.86  (4.37) 0.78  (2.86)
Change at EoT Number Analyzed 168 participants 127 participants
1.40  (3.13) 1.72  (2.84)
Change Within 30 Days of PD Number Analyzed 194 participants 184 participants
1.81  (3.16) 0.89  (2.58)
29.Secondary Outcome
Title Change From Baseline in Treatment Side Effects Burden as Determined by Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-19) General Population 5 (GP5) Item Score
Hide Description The FKSI-19 is a 19-item tool designed to assess the most important symptoms and concerns related to treatment effectiveness in advanced kidney cancer. The FKSI-19 GP5 item (bothered by the side effect of treatment) assessed side effects burden in the past 7 days on a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Repeated measures model-estimated LS mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement.
Time Frame Day 1 and 22 of every cycle (Baseline = Day 1 Cycle 1) up to Cycle 19; Cycle length = 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the PRO-Evaluable Population. Here, 'Number Analyzed' = number of participants evaluable at specified time point.
Arm/Group Title Sunitinib Atezolizumab + Bevacizumab
Hide Arm/Group Description:
Participants received sunitinib at a dose of 50 mg administered orally via capsules once daily on Days 1 to 28 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Participants received atezolizumab at a dose of 1200 mg and bevacizumab at a dose of 15 mg/kg administered via IV infusions on Day 1 and Day 22 of each 42-day cycle until loss of clinical benefit in the opinion of the investigator, unacceptable toxicity or symptomatic deterioration attributed to PD as determined by the investigator, withdrawal of consent, or death, whichever occurred first.
Overall Number of Participants Analyzed 359 373
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Change at Cycle1 Day 22 Number Analyzed 260 participants 301 participants
-1.08  (0.06) -0.36  (0.06)
Change at Cycle 2 Day 1 Number Analyzed 276 participants 305 participants
-0.87  (0.06) -0.45  (0.06)
Change at Cycle 2 Day 22 Number Analyzed 248 participants 283 participants
-1.13  (0.06) -0.43  (0.06)
Change at Cycle 3 Day 1 Number Analyzed 253 participants 297 participants
-1.07  (0.06) -0.49  (0.06)
Change at Cycle 3 Day 22 Number Analyzed 226 participants 279 participants
-1.22  (0.06) -0.45  (0.06)
Change at Cycle 4 Day 1 Number Analyzed 230 participants 266 participants
-1.07  (0.06) -0.45  (0.06)
Change at Cycle 4 Day 22 Number Analyzed 215 participants 252 participants
-1.31  (0.07) -0.49  (0.06)
Change at Cycle 5 Day 1 Number Analyzed 210 participants 238 participants
-1.17  (0.07) -0.52  (0.06)
Change at Cycle 5 Day 22 Number Analyzed 196 participants 238 participants
-1.38  (0.07) -0.55  (0.06)
Change at Cycle 6 Day 1 Number Analyzed 198 participants 223 participants
-1.14  (0.07) -0.51  (0.06)
Change at Cycle 6 Day 22 Number Analyzed 183 participants 207 participants
-1.27  (0.07) -0.56  (0.07)
Change at Cycle 7 Day 1 Number Analyzed 173 participants 200 participants
-1.09  (0.07) -0.61  (0.07)
Change at Cycle 7 Day 22 Number Analyzed 163 participants 191 participants
-1.25  (0.07) -0.58  (0.07)
Change at Cycle 8 Day 1 Number Analyzed 161 participants 191 participants
-1.08  (0.08) -0.61  (0.07)
Change at Cycle 8 Day 22 Number Analyzed 150 participants 186 participants
-1.22  (0.08) -0.62  (0.07)
Change at Cycle 9 Day 1 Number Analyzed 146 participants 185 participants
-1.08  (0.08) -0.60  (0.07)
Change at Cycle 9 Day 22 Number Analyzed 135 participants 172 participants
-1.23  (0.08) -0.52  (0.07)
Change at Cycle 10 Day 1 Number Analyzed 131 participants 169 participants
-1.06  (0.08) -0.53  (0.07)
Change at Cycle 10 Day 22 Number Analyzed 77 participants 150 participants
-1.30  (0.09) -0.57  (0.08)
Change at Cycle 11 Day 1 Number Analyzed 100 participants 134 participants
-1.16  (0.09) -0.52  (0.08)
Change at Cycle 11 Day 22 Number Analyzed 59 participants 122 participants
-1.28  (0.11) -0.54  (0.08)
Change at Cycle 12 Day 1 Number Analyzed 73 participants 110 participants
-1.05  (0.10) -0.62  (0.09)
Change at Cycle 12 Day 22 Number Analyzed 47 participants 93 participants
-1.17  (0.12) -0.56  (0.09)
Change at Cycle 13 Day 1 Number Analyzed 52 participants 81 participants
-1.15  (0.12) -0.62  (0.10)
Change at Cycle 13 Day 22 Number Analyzed 36 participants 72 participants
-1.20  (0.14) -0.64  (0.11)
Change at Cycle 14 Day 1 Number Analyzed 39 participants 57 participants
-0.94  (0.14) -0.61  (0.12)
Change at Cycle 14 Day 22 Number Analyzed 27 participants 54 participants
-1.32  (0.16) -0.65  (0.12)
Change at Cycle 15 Day 1 Number Analyzed 31 participants 43 participants
-0.91  (0.15) -0.62  (0.13)
Change at Cycle 15 Day 22 Number Analyzed 17 participants 36 participants
-1.16  (0.19) -0.72  (0.14)
Change at Cycle 16 Day 1 Number Analyzed 20 participants 27 participants
-1.06  (0.19) -0.58  (0.16)
Change at Cycle 16 Day 22 Number Analyzed 13 participants 22 participants
-1.34  (0.22) -0.41  (0.18)
Change at Cycle 17 Day 1 Number Analyzed 13 participants 19 participants
-1.10  (0.23) -0.56  (0.20)
Change at Cycle 17 Day 22 Number Analyzed 9 participants 11 participants
-1.02  (0.27) -0.44  (0.24)
Change at Cycle 18 Day 1 Number Analyzed 6 participants 9 participants
-1.01  (0.33) -0.38  (0.27)
Change at Cycle 18 Day 22 Number Analyzed 3 participants 6 participants
-0.81  (0.46) -0.48  (0.33)
Change at Cycle 19 Day 1 Number Analyzed 1 participants 5 participants
-1.27  (0.84) -0.75  (0.38)
Change at Cycle 19 Day 22 Number Analyzed 0 participants 2 participants
-0.93  (0.55)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 1 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.58 to 0.87
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 2 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.28 to 0.57
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 2 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.55 to 0.84
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 3 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.44 to 0.73
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 3 Day 22: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.62 to 0.92
Estimation Comments Difference in LS mean score change between arms (Atezolizumab + Bevacizumab minus Sunitinib) was reported.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sunitinib, Atezolizumab + Bevacizumab
Comments Cycle 4 Day 1: Repeated measures model, assuming 1st order autoregressive covariance structure, with a term for visit as a categorical variable, a term for treatment group, a term for treatment-by-visit interaction, baseline score and stratification factors (presence of liver metastasis, PD-L1 status, and Motzer score) included as covariates in the model.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference