Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
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 |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Primary |
Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected Population |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Primary |
Percentage of Participants Who Died of Any Cause in ITT Population |
Percentage of participants who died of any cause was reported. |
Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months) |
|
| Primary |
Overall Survival (OS) in ITT Population |
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. |
Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months) |
|
| Secondary |
Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population |
Percentage of participants who died of any cause was reported. |
Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months) |
|
| Secondary |
OS in PD-L1-Selected Population |
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. |
Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months) |
|
| Secondary |
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 |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
PFS as Determined by an IRC According to RECIST v1.1 in ITT Population |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
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 |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected Population |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
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 |
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. |
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable Population |
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. |
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
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 |
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. |
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable Population |
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. |
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT Population |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT Population |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
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 |
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. |
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable Population |
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. |
Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT Population |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
PFS as Determined by the Investigator According to RECIST v1.1 in ITT Population |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
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 |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid Histology |
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. |
Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) |
|
| Secondary |
Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid Histology |
Percentage of participants with sarcomatoid histology who died of any cause was reported. |
Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months) |
|
| Secondary |
OS in Participants With Sarcomatoid Histology |
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. |
Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months) |
|
| Secondary |
Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II Score |
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. |
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 |
|
| Secondary |
Change From Baseline in Symptom Severity as Determined by MDASI Part I Score |
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. |
Baseline; End of Treatment (EoT) visit (up to approximately 27 months) |
|
| Secondary |
Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale Score |
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. |
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 |
|
| Secondary |
Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue Item |
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. |
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 |
|
| Secondary |
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 |
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. |
Day 1 and 22 of every cycle (Baseline = Day 1 Cycle 1) up to Cycle 19; Cycle length = 42 days |
|
| Secondary |
Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab |
The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against atezolizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result. Here, 'Overall Number of Participants Analyzed' = number of participants with a non-missing baseline ATA sample; 'Number Analyzed' = number of participants with a non-missing ATA sample at indicated timepoint. |
Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycles 2, 4, and 8, and every eight cycles thereafter up to EoT [up to approximately 27 months] and 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days) |
|
| Secondary |
Number of Participants With ATAs Against Bevacizumab |
The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against bevacizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result. |
Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycle 3, at EoT [up to approximately 27 months] and at 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days) |
|
| Secondary |
Maximum Observed Serum Concentration (Cmax) for Atezolizumab |
Cmax for atezolizumab was estimated from plasma concentration versus time data. |
30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days) |
|
| Secondary |
Minimum Observed Serum Concentration (Cmin) for Atezolizumab |
Cmin for atezolizumab was estimated from plasma concentration versus time data. |
Predose (Hour 0) on Day 22 of Cycle 1; predose (Hour 0) on Day 1 of Cycles 2; Cycle length = 42 days |
|
| Secondary |
Cmax for Bevacizumab |
Cmax for bevacizumab was estimated from plasma concentration versus time data. |
30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days) |
|
| Secondary |
Cmin for Bevacizumab |
Cmin for bevacizumab was estimated from plasma concentration versus time data. |
Pre-dose (Hour 0) on Day 1 of Cycle 3 (Cycle length = 42 days) |
|
