Renal Cell Carcinoma
Conditions
Brief summary
This multicenter, randomized, open-label study will evaluate the efficacy, safety and tolerability of atezolizumab as monotherapy or in combination with bevacizumab versus sunitinib in participants with histologically confirmed, inoperable, locally advanced or metastatic renal cell carcinoma who have not received prior systemic therapy either in the adjuvant or metastatic setting.
Interventions
Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.
DRUGBevacizumab
Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.
DRUGSunitinib
Sunitinib will be administered according to the dosage schedule mentioned in the arm description.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unresectable advanced or metastatic renal cell carcinoma with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agents, including treatment in the adjuvant setting * Measurable disease, as defined by RECIST v1.1 * Karnofsky performance score greater than or equal to (\>/=) 70 * Adequate hematologic and end-organ function as defined by protocol * Women of childbearing potential and male participants with partners of childbearing potential must agree to use highly effective methods of contraception as defined by protocol
Exclusion criteria
Disease-Specific Exclusions: * Radiotherapy for renal cell carcinoma within 14 days prior to Cycle 1, Day 1 with the exception of single-fraction radiotherapy given for the indication of pain control * Known active malignancies or metastasis of the brain or spinal cord or leptomeningeal disease, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) * Uncontrolled hypercalcemia or symptomatic hypercalcemia * Malignancies other than renal cell carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death, treated with expected curative outcome General Medical Exclusions: * Life expectancy of less than (\<) 12 weeks * Pregnant and lactating women * History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins * History of autoimmune disease * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan * Participants with active or chronic hepatitis B, active hepatitis C, Human Immunodeficiency Virus (HIV) positive test, significant cardiovascular disease * Prior allogeneic stem cell or solid organ transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS. |
| Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | Progressive Disease (PD): at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm); appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. |
| Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS. |
| Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. |
| PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS. |
| Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. |
| PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS. |
| Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. |
| PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS. |
| Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. |
| PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS. |
| Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. |
| PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS. |
| Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to less than (\<) 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. |
| Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. |
| Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. |
| Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. |
| Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. |
| Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. |
| Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. |
| PFS Per Modified RECIST Via Investigator Assessment in ITT Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS. |
| Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. |
| PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS. |
| Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population | From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR. |
| DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population | From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR. |
| DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR. |
| DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR. |
| DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR. |
| DOR Per Modified RECIST Via Investigator Assessment in ITT Population | From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR. |
| Percentage of Participants Who Died in ITT Population | Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | — |
| Overall Survival (OS) in ITT Population | Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS. |
| OS in IC1/2/3 Population | Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS. |
| Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population | From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. |
| DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population | From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR. |
| Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population | From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. |
| PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population | From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS. |
| Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab | Cycle 1 Day 1 until treatment discontinuation (until data cut-off date 17 October 2016, up to approximately 2.75 years) (1 cycle=6 weeks) | This outcome measure was planned to be analyzed in 'Atezolizumab' and 'Atezolizumab and Bevacizumab' arms only. |
| Maximum Serum Concentration (Cmax) of Atezolizumab | 30 minutes after end of infusion on Cycle 1 Day 1 (1 cycle=6 weeks) (infusion length for first dose=60 minutes) | — |
| Minimum Serum Concentration (Cmin) of Atezolizumab | Pre-infusion (0 hour) on Day 1 of Cycles 2 and 4; Day 22 of Cycles 1, 2, and 4 (1 cycle=6 weeks) (infusion length=30-60 minutes) | — |
| Cmax of Bevacizumab | 30 minutes after end of infusion on Day 1 of Cycles 1 and 2 (1 cycle=6 weeks) (infusion length=30-90 minutes) | — |
| M.D. Anderson Symptom Inventory (MDASI) Interference Score | Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks) | MDASI questionnaire comprises of 2 parts: symptoms (16 items), interference with daily life (6 items). Participants were asked to rate how much their symptoms interfered with general activity, mood, work, relations with other people, walking, and enjoyment of life during the last 24 hours. Each item in the interference score was answered on a scale of 0 (did not interfere) to 10 (interfered completely). The mean score of all 6 items was reported on the scale of 0 (did not interfere) to 10 (interfered completely). |
| Brief Fatigue Inventory (BFI) Fatigue Level Score | Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks) | BFI questionnaire comprises of 2 parts: fatigue level (3 items), interference with daily life (1 item with 6 sub-items). Each items in the fatigue level score was answered on a scale of 0 (no fatigue) to 10 (as bad as you can imagine). The mean score of all 3 items was reported on the scale of 0 (no fatigue) to 10 (as bad as you can imagine). |
| Cmin of Bevacizumab | For Atezolizumab and Bevacizumab Arm: at First-line treatment discontinuation (up to approximately 2.75 years); For Crossover Arms: pre-infusion (0 hour) on Day 1 of Cycle 2 (1 cycle=6 weeks) (infusion length=30-90 minutes) | — |
| Percentage of Participants Who Died in IC1/2/3 Population | Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | — |
| Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. |
| PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) | PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS. |
Other
| Measure | Time frame | Description |
|---|---|---|
| EuroQoL 5 Dimension (EQ-5D) Questionnaire Score | Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks) | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. |
Countries
Czechia, France, Germany, Italy, Poland, Romania, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Total 305 participants enrolled in this study. Participants enrolled in atezolizumab (except European Union \[EU\] participants) or sunitinib group could crossover to receive atezolizumab and bevacizumab combination therapy in case of disease progression. Some participants didn't complete due to study termination, but study was completed as planned.
Participants by arm
| Arm | Count |
|---|---|
| Atezolizumab and Bevacizumab Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) were administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression. | 101 |
| Atezolizumab Atezolizumab 1200 mg was administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination. | 103 |
| Sunitinib Sunitinib 50 mg was administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants could crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination. | 101 |
| Total | 305 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 52 | 50 | 52 |
| Overall Study | Disease Progression | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 0 | 3 |
| Overall Study | Non-Compliance | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Sponsor Decision | 1 | 0 | 0 |
| Overall Study | Study terminated by Sponsor | 38 | 50 | 34 |
| Overall Study | Withdrawal by Subject | 5 | 3 | 10 |
Baseline characteristics
| Characteristic | Atezolizumab and Bevacizumab | Atezolizumab | Sunitinib | Total |
|---|---|---|---|---|
| Age, Continuous | 61.1 years STANDARD_DEVIATION 10.8 | 60.1 years STANDARD_DEVIATION 10.2 | 59.7 years STANDARD_DEVIATION 10.8 | 60.3 years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 27 Participants | 26 Participants | 22 Participants | 75 Participants |
| Sex: Female, Male Male | 74 Participants | 77 Participants | 79 Participants | 230 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 99 / 101 | 94 / 103 | 99 / 100 | 44 / 46 | 57 / 63 |
| serious Total, serious adverse events | 49 / 101 | 37 / 103 | 28 / 100 | 15 / 46 | 22 / 63 |
Outcome results
Primary
Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population included ITT participants with programmed death-ligand 1 (PD-L1) expression of greater than or equal to (\>=) 1% on tumor-infiltrating immune cells.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population | 58.0 percentage of participants |
| Atezolizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population | 59.3 percentage of participants |
| Sunitinib | Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population | 68.3 percentage of participants |
Primary
Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population
Progressive Disease (PD): at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm); appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population | 66.3 percentage of participants |
| Atezolizumab | Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population | 59.2 percentage of participants |
| Sunitinib | Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population | 58.4 percentage of participants |
Primary
PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | 14.7 months |
| Atezolizumab | PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | 5.5 months |
| Sunitinib | PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | 7.8 months |
p-value: 0.095295% CI: [0.38, 1.08]Log Rank
p-value: 0.917295% CI: [0.63, 1.67]Log Rank
Primary
Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population | 11.7 months |
| Atezolizumab | Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population | 6.1 months |
| Sunitinib | Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population | 8.4 months |
p-value: 0.981995% CI: [0.69, 1.45]Log Rank
p-value: 0.35895% CI: [0.82, 1.71]Log Rank
Secondary
Brief Fatigue Inventory (BFI) Fatigue Level Score
BFI questionnaire comprises of 2 parts: fatigue level (3 items), interference with daily life (1 item with 6 sub-items). Each items in the fatigue level score was answered on a scale of 0 (no fatigue) to 10 (as bad as you can imagine). The mean score of all 3 items was reported on the scale of 0 (no fatigue) to 10 (as bad as you can imagine).
Time frame: Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)
Population: PRO-evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure. 'Number Analyzed'=participants evaluable for this outcome measure at specified timepoint for each arm respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 9 Day 22 | 2.80 units on a scale | Standard Deviation 2.73 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 23 Day 22 | 2.00 units on a scale | Standard Deviation 2.83 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 15 Day 1 | 2.73 units on a scale | Standard Deviation 2.56 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 9 Day 1 | 3.09 units on a scale | Standard Deviation 2.81 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 24 Day 1 | 4.00 units on a scale | — |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 14 Day 1 | 2.94 units on a scale | Standard Deviation 2.94 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 8 Day 22 | 2.88 units on a scale | Standard Deviation 2.8 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 1 Day 1 | 2.80 units on a scale | Standard Deviation 2.64 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 8 Day 1 | 2.80 units on a scale | Standard Deviation 2.56 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 19 Day 22 | 1.90 units on a scale | Standard Deviation 2.42 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 7 Day 22 | 2.86 units on a scale | Standard Deviation 2.6 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 7 Day 1 | 3.16 units on a scale | Standard Deviation 2.81 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 1 Day 22 | 3.80 units on a scale | Standard Deviation 2.86 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 17 Day 22 | 2.00 units on a scale | Standard Deviation 1.8 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 6 Day 22 | 3.23 units on a scale | Standard Deviation 2.94 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 2 Day 1 | 3.21 units on a scale | Standard Deviation 2.61 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 13 Day 22 | 2.97 units on a scale | Standard Deviation 2.97 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 6 Day 1 | 3.05 units on a scale | Standard Deviation 2.83 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 2 Day 22 | 3.15 units on a scale | Standard Deviation 2.61 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 20 Day 1 | 3.00 units on a scale | Standard Deviation 3.16 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 5 Day 22 | 3.02 units on a scale | Standard Deviation 2.87 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 3 Day 1 | 2.91 units on a scale | Standard Deviation 2.6 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 10 Day 22 | 2.91 units on a scale | Standard Deviation 2.83 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 5 Day 1 | 2.97 units on a scale | Standard Deviation 2.83 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 3 Day 22 | 2.93 units on a scale | Standard Deviation 2.67 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 13 Day 1 | 2.69 units on a scale | Standard Deviation 2.57 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 4 Day 22 | 3.06 units on a scale | Standard Deviation 2.68 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 4 Day 1 | 3.21 units on a scale | Standard Deviation 2.66 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 20 Day 22 | 2.40 units on a scale | Standard Deviation 3.05 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 16 Day 22 | 1.70 units on a scale | Standard Deviation 1.61 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 22 Day 22 | 1.33 units on a scale | Standard Deviation 2.31 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 17 Day 1 | 1.78 units on a scale | Standard Deviation 1.59 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 12 Day 22 | 2.79 units on a scale | Standard Deviation 2.46 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 23 Day 1 | 2.50 units on a scale | Standard Deviation 3.54 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 16 Day 1 | 1.88 units on a scale | Standard Deviation 1.99 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Treatment discontinuation | 3.74 units on a scale | Standard Deviation 2.82 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 18 Day 1 | 2.23 units on a scale | Standard Deviation 1.74 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 18 Day 22 | 1.92 units on a scale | Standard Deviation 2.14 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 12 Day 1 | 2.31 units on a scale | Standard Deviation 2.25 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 21 Day 1 | 2.60 units on a scale | Standard Deviation 2.97 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 11 Day 22 | 2.59 units on a scale | Standard Deviation 2.44 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 21 Day 22 | 2.40 units on a scale | Standard Deviation 1.95 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 15 Day 22 | 2.61 units on a scale | Standard Deviation 2.79 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 11 Day 1 | 2.98 units on a scale | Standard Deviation 2.71 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 22 Day 1 | 1.25 units on a scale | Standard Deviation 1.89 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 14 Day 22 | 2.83 units on a scale | Standard Deviation 2.85 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 10 Day 1 | 2.80 units on a scale | Standard Deviation 2.58 |
| Atezolizumab and Bevacizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 19 Day 1 | 2.17 units on a scale | Standard Deviation 2.48 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 24 Day 22 | 0.00 units on a scale | — |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 1 Day 1 | 2.52 units on a scale | Standard Deviation 2.72 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 5 Day 1 | 1.59 units on a scale | Standard Deviation 2.03 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 10 Day 22 | 1.33 units on a scale | Standard Deviation 1.9 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 13 Day 22 | 1.55 units on a scale | Standard Deviation 2.13 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 15 Day 1 | 1.76 units on a scale | Standard Deviation 2.19 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 16 Day 22 | 2.11 units on a scale | Standard Deviation 2.15 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 17 Day 22 | 2.13 units on a scale | Standard Deviation 2.42 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 18 Day 1 | 1.88 units on a scale | Standard Deviation 2.23 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 18 Day 22 | 1.67 units on a scale | Standard Deviation 2.07 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 19 Day 1 | 1.50 units on a scale | Standard Deviation 1.97 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 19 Day 22 | 1.40 units on a scale | Standard Deviation 2.19 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 20 Day 1 | 1.25 units on a scale | Standard Deviation 2.5 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 21 Day 1 | 2.50 units on a scale | Standard Deviation 3.54 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 22 Day 22 | 0.00 units on a scale | — |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 25 Day 1 | 0.00 units on a scale | — |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 20 Day 22 | 1.50 units on a scale | Standard Deviation 3 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 21 Day 22 | 0.00 units on a scale | — |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 22 Day 1 | 0.00 units on a scale | — |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 23 Day 1 | 0.00 units on a scale | — |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 23 Day 22 | 0.00 units on a scale | — |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 24 Day 1 | 0.00 units on a scale | — |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Treatment discontinuation | 3.95 units on a scale | Standard Deviation 3.27 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 1 Day 22 | 2.55 units on a scale | Standard Deviation 2.6 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 2 Day 1 | 2.63 units on a scale | Standard Deviation 2.69 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 2 Day 22 | 2.57 units on a scale | Standard Deviation 2.74 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 3 Day 1 | 2.11 units on a scale | Standard Deviation 2.42 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 3 Day 22 | 2.31 units on a scale | Standard Deviation 2.71 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 4 Day 1 | 2.32 units on a scale | Standard Deviation 2.86 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 4 Day 22 | 2.33 units on a scale | Standard Deviation 2.94 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 5 Day 22 | 1.34 units on a scale | Standard Deviation 1.81 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 6 Day 1 | 1.42 units on a scale | Standard Deviation 1.9 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 6 Day 22 | 1.39 units on a scale | Standard Deviation 2.01 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 7 Day 1 | 1.33 units on a scale | Standard Deviation 1.91 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 7 Day 22 | 1.24 units on a scale | Standard Deviation 1.67 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 8 Day 1 | 1.12 units on a scale | Standard Deviation 1.68 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 8 Day 22 | 1.24 units on a scale | Standard Deviation 1.75 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 9 Day 1 | 1.11 units on a scale | Standard Deviation 1.55 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 9 Day 22 | 1.19 units on a scale | Standard Deviation 1.71 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 10 Day 1 | 1.29 units on a scale | Standard Deviation 1.88 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 11 Day 1 | 1.40 units on a scale | Standard Deviation 1.96 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 11 Day 22 | 1.72 units on a scale | Standard Deviation 2.23 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 12 Day 1 | 1.25 units on a scale | Standard Deviation 1.96 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 12 Day 22 | 1.44 units on a scale | Standard Deviation 2.12 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 13 Day 1 | 1.65 units on a scale | Standard Deviation 2.17 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 14 Day 1 | 1.45 units on a scale | Standard Deviation 2.14 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 14 Day 22 | 1.61 units on a scale | Standard Deviation 2 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 15 Day 22 | 0.92 units on a scale | Standard Deviation 1.12 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 16 Day 1 | 1.54 units on a scale | Standard Deviation 2.07 |
| Atezolizumab | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 17 Day 1 | 1.60 units on a scale | Standard Deviation 1.96 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 24 Day 22 | 0.00 units on a scale | — |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 17 Day 22 | 2.38 units on a scale | Standard Deviation 1.6 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 8 Day 1 | 1.72 units on a scale | Standard Deviation 1.7 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 24 Day 1 | 2.00 units on a scale | — |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 14 Day 1 | 2.30 units on a scale | Standard Deviation 2.34 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 8 Day 22 | 2.58 units on a scale | Standard Deviation 2.13 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 23 Day 22 | 4.50 units on a scale | Standard Deviation 3.54 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 18 Day 22 | 2.14 units on a scale | Standard Deviation 2.19 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 9 Day 1 | 2.12 units on a scale | Standard Deviation 2.48 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 23 Day 1 | 2.00 units on a scale | Standard Deviation 2.83 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 16 Day 22 | 2.85 units on a scale | Standard Deviation 2.19 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 9 Day 22 | 2.64 units on a scale | Standard Deviation 2.57 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 22 Day 1 | 2.00 units on a scale | Standard Deviation 1.41 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 14 Day 22 | 2.60 units on a scale | Standard Deviation 2.09 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 10 Day 1 | 2.11 units on a scale | Standard Deviation 2.23 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 10 Day 22 | 2.24 units on a scale | Standard Deviation 2.43 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 21 Day 22 | 2.00 units on a scale | Standard Deviation 1.41 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 15 Day 1 | 2.60 units on a scale | Standard Deviation 2.33 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 11 Day 1 | 1.93 units on a scale | Standard Deviation 1.65 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 21 Day 1 | 1.67 units on a scale | Standard Deviation 1.53 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 15 Day 22 | 2.94 units on a scale | Standard Deviation 1.61 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 11 Day 22 | 2.42 units on a scale | Standard Deviation 2.12 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 20 Day 22 | 2.25 units on a scale | Standard Deviation 2.06 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 18 Day 1 | 1.71 units on a scale | Standard Deviation 1.7 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 12 Day 1 | 1.66 units on a scale | Standard Deviation 1.67 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 22 Day 22 | 3.00 units on a scale | Standard Deviation 2.83 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 17 Day 1 | 1.50 units on a scale | Standard Deviation 1.51 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 12 Day 22 | 2.27 units on a scale | Standard Deviation 2.05 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 4 Day 1 | 2.39 units on a scale | Standard Deviation 2.47 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 3 Day 22 | 3.60 units on a scale | Standard Deviation 3.09 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 20 Day 1 | 1.80 units on a scale | Standard Deviation 1.3 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 4 Day 22 | 3.15 units on a scale | Standard Deviation 2.57 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 3 Day 1 | 2.35 units on a scale | Standard Deviation 2.44 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 5 Day 1 | 2.32 units on a scale | Standard Deviation 2.62 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 2 Day 22 | 3.69 units on a scale | Standard Deviation 2.74 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 16 Day 1 | 2.21 units on a scale | Standard Deviation 2.42 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 5 Day 22 | 2.91 units on a scale | Standard Deviation 2.86 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 2 Day 1 | 2.86 units on a scale | Standard Deviation 2.76 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 13 Day 1 | 2.08 units on a scale | Standard Deviation 1.56 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 6 Day 1 | 2.22 units on a scale | Standard Deviation 2.48 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 1 Day 22 | 4.42 units on a scale | Standard Deviation 3.09 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 19 Day 22 | 3.29 units on a scale | Standard Deviation 2.43 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 6 Day 22 | 3.09 units on a scale | Standard Deviation 2.69 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 1 Day 1 | 2.66 units on a scale | Standard Deviation 2.74 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 13 Day 22 | 2.60 units on a scale | Standard Deviation 2.28 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 7 Day 1 | 1.68 units on a scale | Standard Deviation 1.75 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Treatment discontinuation | 3.75 units on a scale | Standard Deviation 3.09 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 19 Day 1 | 2.29 units on a scale | Standard Deviation 3.3 |
| Sunitinib | Brief Fatigue Inventory (BFI) Fatigue Level Score | Cycle 7 Day 22 | 2.16 units on a scale | Standard Deviation 1.87 |
Secondary
Cmax of Bevacizumab
Time frame: 30 minutes after end of infusion on Day 1 of Cycles 1 and 2 (1 cycle=6 weeks) (infusion length=30-90 minutes)
Population: PK evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atezolizumab and Bevacizumab | Cmax of Bevacizumab | 89.8 mcg/mL | Standard Deviation 39.4 |
| Atezolizumab | Cmax of Bevacizumab | 433 mcg/mL | Standard Deviation 115 |
| Sunitinib | Cmax of Bevacizumab | 455 mcg/mL | Standard Deviation 106 |
Secondary
Cmin of Bevacizumab
Time frame: For Atezolizumab and Bevacizumab Arm: at First-line treatment discontinuation (up to approximately 2.75 years); For Crossover Arms: pre-infusion (0 hour) on Day 1 of Cycle 2 (1 cycle=6 weeks) (infusion length=30-90 minutes)
Population: PK evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atezolizumab and Bevacizumab | Cmin of Bevacizumab | 75.2 mcg/mL | Standard Deviation 72.1 |
| Atezolizumab | Cmin of Bevacizumab | 101 mcg/mL | Standard Deviation 48.7 |
| Sunitinib | Cmin of Bevacizumab | 95.9 mcg/mL | Standard Deviation 43.9 |
Secondary
DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.
Time frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | 22.4 months |
| Atezolizumab | DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | NA months |
| Sunitinib | DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | 16.6 months |
Secondary
DOR Per Modified RECIST Via Investigator Assessment in ITT Population
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.
Time frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | DOR Per Modified RECIST Via Investigator Assessment in ITT Population | NA months |
| Atezolizumab | DOR Per Modified RECIST Via Investigator Assessment in ITT Population | NA months |
| Sunitinib | DOR Per Modified RECIST Via Investigator Assessment in ITT Population | 16.6 months |
Secondary
DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Time frame: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Crossover population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population | NA months |
| Atezolizumab | DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population | NA months |
Secondary
DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Time frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | 22.4 months |
| Atezolizumab | DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | NA months |
| Sunitinib | DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | 14.1 months |
Secondary
DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Time frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population | NA months |
| Atezolizumab | DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population | NA months |
| Sunitinib | DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population | 14.2 months |
Secondary
DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Time frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | 22.1 months |
| Atezolizumab | DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | NA months |
| Sunitinib | DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | NA months |
Secondary
Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population
DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.
Time frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population | 22.1 months |
| Atezolizumab | Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population | NA months |
| Sunitinib | Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population | NA months |
Secondary
Maximum Serum Concentration (Cmax) of Atezolizumab
Time frame: 30 minutes after end of infusion on Cycle 1 Day 1 (1 cycle=6 weeks) (infusion length for first dose=60 minutes)
Population: The pharmacokinetic (PK) evaluable population included participants who received at least one dose of study drug and had sufficient PK sample collected within the time specified in the protocol. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atezolizumab and Bevacizumab | Maximum Serum Concentration (Cmax) of Atezolizumab | 335 micrograms per milliliter (mcg/mL) | Standard Deviation 86 |
| Atezolizumab | Maximum Serum Concentration (Cmax) of Atezolizumab | 358 micrograms per milliliter (mcg/mL) | Standard Deviation 93.1 |
| Sunitinib | Maximum Serum Concentration (Cmax) of Atezolizumab | 418 micrograms per milliliter (mcg/mL) | Standard Deviation 114 |
| Sunitinib (Crossover) | Maximum Serum Concentration (Cmax) of Atezolizumab | 314 micrograms per milliliter (mcg/mL) | Standard Deviation 87.1 |
Secondary
M.D. Anderson Symptom Inventory (MDASI) Interference Score
MDASI questionnaire comprises of 2 parts: symptoms (16 items), interference with daily life (6 items). Participants were asked to rate how much their symptoms interfered with general activity, mood, work, relations with other people, walking, and enjoyment of life during the last 24 hours. Each item in the interference score was answered on a scale of 0 (did not interfere) to 10 (interfered completely). The mean score of all 6 items was reported on the scale of 0 (did not interfere) to 10 (interfered completely).
Time frame: Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)
Population: Patient Reported Outcome (PRO)-evaluable population: randomized participants who had non-missing baseline assessment and at least 1 post-baseline assessment. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome. 'Number Analyzed'=participants evaluable for this outcome at specified timepoint for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 20 Day 1 | 1.19 units on a scale | Standard Deviation 1.31 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 5 Day 22 | 1.80 units on a scale | Standard Deviation 2.29 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 6 Day 1 | 1.91 units on a scale | Standard Deviation 2.54 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 19 Day 22 | 0.97 units on a scale | Standard Deviation 1.37 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 8 Day 22 | 1.81 units on a scale | Standard Deviation 2.41 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 10 Day 22 | 1.55 units on a scale | Standard Deviation 2.09 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 19 Day 1 | 1.11 units on a scale | Standard Deviation 1.25 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 9 Day 1 | 1.75 units on a scale | Standard Deviation 2.24 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 24 Day 1 | 2.33 units on a scale | — |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 18 Day 22 | 0.79 units on a scale | Standard Deviation 1.06 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 9 Day 22 | 1.64 units on a scale | Standard Deviation 2.16 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 6 Day 22 | 1.80 units on a scale | Standard Deviation 2.38 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 18 Day 1 | 0.93 units on a scale | Standard Deviation 1.07 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 10 Day 1 | 1.43 units on a scale | Standard Deviation 1.82 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 11 Day 22 | 1.35 units on a scale | Standard Deviation 1.81 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 22 Day 1 | 0.54 units on a scale | Standard Deviation 0.76 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 8 Day 1 | 1.88 units on a scale | Standard Deviation 2.26 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 11 Day 1 | 1.65 units on a scale | Standard Deviation 2.13 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 7 Day 1 | 1.99 units on a scale | Standard Deviation 2.49 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 13 Day 22 | 1.45 units on a scale | Standard Deviation 2.32 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 1 Day 1 | 1.60 units on a scale | Standard Deviation 1.97 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 13 Day 1 | 1.50 units on a scale | Standard Deviation 2.16 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 12 Day 1 | 1.21 units on a scale | Standard Deviation 1.69 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 21 Day 22 | 1.23 units on a scale | Standard Deviation 1.51 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 12 Day 22 | 1.51 units on a scale | Standard Deviation 2.23 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 14 Day 1 | 1.60 units on a scale | Standard Deviation 2.24 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 17 Day 22 | 0.73 units on a scale | Standard Deviation 1.02 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 1 Day 22 | 2.08 units on a scale | Standard Deviation 2.34 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 7 Day 22 | 2.01 units on a scale | Standard Deviation 2.45 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 17 Day 1 | 0.98 units on a scale | Standard Deviation 0.99 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 2 Day 1 | 1.56 units on a scale | Standard Deviation 1.82 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 15 Day 22 | 1.48 units on a scale | Standard Deviation 1.92 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 16 Day 22 | 0.72 units on a scale | Standard Deviation 0.93 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 2 Day 22 | 1.57 units on a scale | Standard Deviation 1.83 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 5 Day 1 | 1.70 units on a scale | Standard Deviation 2.29 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 16 Day 1 | 0.87 units on a scale | Standard Deviation 0.99 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 3 Day 1 | 1.72 units on a scale | Standard Deviation 2.15 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 15 Day 1 | 1.16 units on a scale | Standard Deviation 1.74 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 3 Day 22 | 1.66 units on a scale | Standard Deviation 2.07 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 23 Day 1 | 1.67 units on a scale | Standard Deviation 1.89 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 14 Day 22 | 1.40 units on a scale | Standard Deviation 2.09 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 4 Day 1 | 1.59 units on a scale | Standard Deviation 2.11 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 23 Day 22 | 1.25 units on a scale | Standard Deviation 1.77 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 20 Day 22 | 1.10 units on a scale | Standard Deviation 1.3 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 4 Day 22 | 1.68 units on a scale | Standard Deviation 2.31 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Treatment discontinuation | 2.54 units on a scale | Standard Deviation 2.66 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 21 Day 1 | 1.17 units on a scale | Standard Deviation 1.42 |
| Atezolizumab and Bevacizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 22 Day 22 | 0.94 units on a scale | Standard Deviation 1.07 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 3 Day 1 | 0.90 units on a scale | Standard Deviation 1.43 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 7 Day 1 | 0.53 units on a scale | Standard Deviation 0.78 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 7 Day 22 | 0.59 units on a scale | Standard Deviation 0.93 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 14 Day 1 | 0.67 units on a scale | Standard Deviation 0.95 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 16 Day 1 | 0.85 units on a scale | Standard Deviation 1.4 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 25 Day 1 | 0.00 units on a scale | — |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 6 Day 1 | 0.64 units on a scale | Standard Deviation 1.13 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 6 Day 22 | 0.63 units on a scale | Standard Deviation 1.12 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 1 Day 1 | 1.38 units on a scale | Standard Deviation 2.03 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 1 Day 22 | 1.26 units on a scale | Standard Deviation 2.07 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 2 Day 1 | 1.20 units on a scale | Standard Deviation 1.72 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 2 Day 22 | 1.04 units on a scale | Standard Deviation 1.62 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 3 Day 22 | 1.01 units on a scale | Standard Deviation 1.58 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 4 Day 1 | 1.24 units on a scale | Standard Deviation 1.99 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 4 Day 22 | 1.26 units on a scale | Standard Deviation 1.98 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 5 Day 1 | 0.69 units on a scale | Standard Deviation 1.11 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 5 Day 22 | 0.67 units on a scale | Standard Deviation 1.33 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 8 Day 22 | 0.58 units on a scale | Standard Deviation 0.91 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 9 Day 1 | 0.55 units on a scale | Standard Deviation 0.9 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 9 Day 22 | 0.58 units on a scale | Standard Deviation 0.89 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 10 Day 1 | 0.81 units on a scale | Standard Deviation 1.13 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 10 Day 22 | 0.70 units on a scale | Standard Deviation 1.1 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 11 Day 1 | 0.61 units on a scale | Standard Deviation 0.95 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 11 Day 22 | 0.78 units on a scale | Standard Deviation 1.07 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 12 Day 1 | 0.68 units on a scale | Standard Deviation 1.15 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 12 Day 22 | 0.53 units on a scale | Standard Deviation 0.99 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 13 Day 1 | 0.68 units on a scale | Standard Deviation 1.07 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 13 Day 22 | 0.67 units on a scale | Standard Deviation 1.1 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 8 Day 1 | 0.55 units on a scale | Standard Deviation 0.85 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 18 Day 1 | 0.71 units on a scale | Standard Deviation 0.98 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 18 Day 22 | 0.33 units on a scale | Standard Deviation 0.41 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 19 Day 1 | 0.31 units on a scale | Standard Deviation 0.34 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 19 Day 22 | 0.30 units on a scale | Standard Deviation 0.41 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 20 Day 1 | 0.21 units on a scale | Standard Deviation 0.42 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 21 Day 1 | 0.00 units on a scale | Standard Deviation 0 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 20 Day 22 | 0.04 units on a scale | Standard Deviation 0.08 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 14 Day 22 | 0.63 units on a scale | Standard Deviation 0.94 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 15 Day 1 | 0.84 units on a scale | Standard Deviation 1.16 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 15 Day 22 | 0.71 units on a scale | Standard Deviation 1.1 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 16 Day 22 | 0.87 units on a scale | Standard Deviation 1.3 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 17 Day 1 | 0.57 units on a scale | Standard Deviation 0.75 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 17 Day 22 | 0.65 units on a scale | Standard Deviation 0.97 |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 21 Day 22 | 0.00 units on a scale | — |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 22 Day 1 | 0.00 units on a scale | — |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 24 Day 1 | 0.00 units on a scale | — |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 22 Day 22 | 0.00 units on a scale | — |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 23 Day 1 | 0.00 units on a scale | — |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 23 Day 22 | 0.00 units on a scale | — |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 24 Day 22 | 0.00 units on a scale | — |
| Atezolizumab | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Treatment discontinuation | 2.29 units on a scale | Standard Deviation 2.54 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 10 Day 1 | 1.08 units on a scale | Standard Deviation 1.4 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 20 Day 22 | 1.67 units on a scale | Standard Deviation 1.56 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 4 Day 22 | 1.92 units on a scale | Standard Deviation 2 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 6 Day 1 | 1.39 units on a scale | Standard Deviation 1.76 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 20 Day 1 | 0.90 units on a scale | Standard Deviation 1.07 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 4 Day 1 | 1.61 units on a scale | Standard Deviation 2.24 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 24 Day 22 | 0.50 units on a scale | — |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 14 Day 1 | 1.07 units on a scale | Standard Deviation 1.31 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 3 Day 22 | 2.20 units on a scale | Standard Deviation 2.42 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 22 Day 1 | 0.83 units on a scale | Standard Deviation 0.71 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 14 Day 22 | 1.50 units on a scale | Standard Deviation 1.48 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 3 Day 1 | 1.49 units on a scale | Standard Deviation 2.01 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 5 Day 22 | 1.97 units on a scale | Standard Deviation 2.21 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 15 Day 1 | 1.50 units on a scale | Standard Deviation 1.64 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 24 Day 1 | 1.67 units on a scale | — |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 15 Day 22 | 2.08 units on a scale | Standard Deviation 1.64 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 2 Day 22 | 2.50 units on a scale | Standard Deviation 2.47 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 16 Day 1 | 1.07 units on a scale | Standard Deviation 1.22 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 2 Day 1 | 1.83 units on a scale | Standard Deviation 2.19 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 22 Day 22 | 1.25 units on a scale | Standard Deviation 1.53 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 16 Day 22 | 2.04 units on a scale | Standard Deviation 2.24 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 1 Day 22 | 3.16 units on a scale | Standard Deviation 2.65 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 18 Day 1 | 0.95 units on a scale | Standard Deviation 1.15 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 17 Day 1 | 0.71 units on a scale | Standard Deviation 0.95 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 12 Day 1 | 0.84 units on a scale | Standard Deviation 0.83 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 1 Day 1 | 1.79 units on a scale | Standard Deviation 2.39 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 12 Day 22 | 1.41 units on a scale | Standard Deviation 1.53 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 11 Day 22 | 1.47 units on a scale | Standard Deviation 1.61 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Treatment discontinuation | 3.49 units on a scale | Standard Deviation 3.16 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 13 Day 1 | 1.26 units on a scale | Standard Deviation 1.45 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 11 Day 1 | 0.98 units on a scale | Standard Deviation 1 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 21 Day 1 | 0.78 units on a scale | Standard Deviation 1.07 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 13 Day 22 | 1.32 units on a scale | Standard Deviation 1.37 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 7 Day 22 | 1.15 units on a scale | Standard Deviation 1.04 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 10 Day 22 | 1.49 units on a scale | Standard Deviation 1.78 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 23 Day 22 | 2.67 units on a scale | Standard Deviation 2.36 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 17 Day 22 | 1.21 units on a scale | Standard Deviation 1.32 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 9 Day 22 | 1.57 units on a scale | Standard Deviation 1.61 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 7 Day 1 | 1.00 units on a scale | Standard Deviation 1.09 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 9 Day 1 | 1.16 units on a scale | Standard Deviation 1.22 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 23 Day 1 | 1.58 units on a scale | Standard Deviation 2 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 18 Day 22 | 1.05 units on a scale | Standard Deviation 1.42 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 8 Day 22 | 1.34 units on a scale | Standard Deviation 1.39 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 21 Day 22 | 1.25 units on a scale | Standard Deviation 1.53 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 19 Day 1 | 1.33 units on a scale | Standard Deviation 1.66 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 8 Day 1 | 0.94 units on a scale | Standard Deviation 1.04 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 6 Day 22 | 2.00 units on a scale | Standard Deviation 2.23 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 19 Day 22 | 1.55 units on a scale | Standard Deviation 1.69 |
| Sunitinib | M.D. Anderson Symptom Inventory (MDASI) Interference Score | Cycle 5 Day 1 | 1.53 units on a scale | Standard Deviation 1.96 |
Secondary
Minimum Serum Concentration (Cmin) of Atezolizumab
Time frame: Pre-infusion (0 hour) on Day 1 of Cycles 2 and 4; Day 22 of Cycles 1, 2, and 4 (1 cycle=6 weeks) (infusion length=30-60 minutes)
Population: PK evaluable population. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure. 'Number Analyzed'=participants evaluable for this outcome measure at specified timepoint for each arm respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atezolizumab and Bevacizumab | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 Day 1 | 122 mcg/mL | Standard Deviation 50.4 |
| Atezolizumab and Bevacizumab | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 4 Day 22 | 190 mcg/mL | Standard Deviation 86.3 |
| Atezolizumab and Bevacizumab | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 Day 22 | 152 mcg/mL | Standard Deviation 65.3 |
| Atezolizumab and Bevacizumab | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 1 Day 22 | 72.6 mcg/mL | Standard Deviation 29.5 |
| Atezolizumab and Bevacizumab | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 4 Day 1 | 183 mcg/mL | Standard Deviation 90.5 |
| Atezolizumab | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 1 Day 22 | 79.9 mcg/mL | Standard Deviation 26.1 |
| Atezolizumab | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 Day 1 | 125 mcg/mL | Standard Deviation 47.4 |
| Atezolizumab | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 Day 22 | 159 mcg/mL | Standard Deviation 84.6 |
| Atezolizumab | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 4 Day 22 | 200 mcg/mL | Standard Deviation 90 |
| Atezolizumab | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 4 Day 1 | 192 mcg/mL | Standard Deviation 77.6 |
| Sunitinib | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 1 Day 22 | 174 mcg/mL | Standard Deviation 121 |
| Sunitinib | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 4 Day 1 | 154 mcg/mL | Standard Deviation 62.7 |
| Sunitinib | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 4 Day 22 | 163 mcg/mL | Standard Deviation 70.5 |
| Sunitinib | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 Day 1 | 158 mcg/mL | Standard Deviation 101 |
| Sunitinib | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 Day 22 | 164 mcg/mL | Standard Deviation 70.7 |
| Sunitinib (Crossover) | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 Day 1 | 106 mcg/mL | Standard Deviation 45.2 |
| Sunitinib (Crossover) | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 4 Day 22 | 172 mcg/mL | Standard Deviation 78.8 |
| Sunitinib (Crossover) | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 4 Day 1 | 174 mcg/mL | Standard Deviation 75.7 |
| Sunitinib (Crossover) | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 1 Day 22 | 73.2 mcg/mL | Standard Deviation 31.5 |
| Sunitinib (Crossover) | Minimum Serum Concentration (Cmin) of Atezolizumab | Cycle 2 Day 22 | 141 mcg/mL | Standard Deviation 85.5 |
Secondary
OS in IC1/2/3 Population
OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.
Time frame: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | OS in IC1/2/3 Population | 27.3 months |
| Atezolizumab | OS in IC1/2/3 Population | 30.2 months |
| Sunitinib | OS in IC1/2/3 Population | NA months |
p-value: 0.787995% CI: [0.47, 1.78]Log Rank
p-value: 0.906595% CI: [0.52, 1.8]Log Rank
Secondary
Overall Survival (OS) in ITT Population
OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.
Time frame: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | Overall Survival (OS) in ITT Population | NA months |
| Atezolizumab | Overall Survival (OS) in ITT Population | NA months |
| Sunitinib | Overall Survival (OS) in ITT Population | NA months |
p-value: 0.286795% CI: [0.8, 2.13]Log Rank
p-value: 0.803995% CI: [0.65, 1.73]Log Rank
Secondary
Percentage of Participants Who Died in IC1/2/3 Population
Time frame: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants Who Died in IC1/2/3 Population | 38.0 percentage of participants |
| Atezolizumab | Percentage of Participants Who Died in IC1/2/3 Population | 39.8 percentage of participants |
| Sunitinib | Percentage of Participants Who Died in IC1/2/3 Population | 35.0 percentage of participants |
Secondary
Percentage of Participants Who Died in ITT Population
Time frame: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants Who Died in ITT Population | 38.6 percentage of participants |
| Atezolizumab | Percentage of Participants Who Died in ITT Population | 35.0 percentage of participants |
| Sunitinib | Percentage of Participants Who Died in ITT Population | 30.7 percentage of participants |
Secondary
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab
This outcome measure was planned to be analyzed in 'Atezolizumab' and 'Atezolizumab and Bevacizumab' arms only.
Time frame: Cycle 1 Day 1 until treatment discontinuation (until data cut-off date 17 October 2016, up to approximately 2.75 years) (1 cycle=6 weeks)
Population: ATA evaluable population included participants at baseline who had a baseline ATA sample and post-baseline participants who had at least one ATA sample and had received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab | 34.0 percentage of participants |
| Atezolizumab | Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab | 25.0 percentage of participants |
Secondary
Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population
PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population | 52.0 percentage of participants |
| Atezolizumab | Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population | 59.3 percentage of participants |
| Sunitinib | Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population | 75.0 percentage of participants |
Secondary
Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population
PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population | 60.4 percentage of participants |
| Atezolizumab | Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population | 61.2 percentage of participants |
| Sunitinib | Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population | 63.4 percentage of participants |
Secondary
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time frame: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Crossover population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population | 59.1 percentage of participants |
| Atezolizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population | 68.4 percentage of participants |
Secondary
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population | 66.0 percentage of participants |
| Atezolizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population | 74.1 percentage of participants |
| Sunitinib | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population | 81.7 percentage of participants |
Secondary
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population | 71.3 percentage of participants |
| Atezolizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population | 75.7 percentage of participants |
| Sunitinib | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population | 75.2 percentage of participants |
Secondary
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Biomarker evaluable population. Participants with higher than median expression of an immune gene signature were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 57.8 percentage of participants |
| Atezolizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 77.3 percentage of participants |
| Sunitinib | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 83.3 percentage of participants |
Secondary
Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 63.9 percentage of participants |
| Atezolizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 76.4 percentage of participants |
| Sunitinib | Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 78.3 percentage of participants |
Secondary
Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Biomarker evaluable population included ITT participants whose tumor samples had sufficient material available for gene signature expression analyses. Participants with higher than median expression of an immune gene signature were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 55.6 percentage of participants |
| Atezolizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 61.4 percentage of participants |
| Sunitinib | Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 73.8 percentage of participants |
Secondary
Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 59.0 percentage of participants |
| Atezolizumab | Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 58.2 percentage of participants |
| Sunitinib | Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 65.0 percentage of participants |
Secondary
Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to less than (\<) 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population | 31.7 percentage of participants |
| Atezolizumab | Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population | 25.2 percentage of participants |
| Sunitinib | Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population | 28.7 percentage of participants |
p-value: 0.649295% CI: [-10.68, 16.62]Cochran-Mantel-Haenszel
p-value: 0.543395% CI: [-16.63, 9.69]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | 52.0 percentage of participants |
| Atezolizumab | Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | 27.8 percentage of participants |
| Sunitinib | Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | 30.0 percentage of participants |
p-value: 0.011195% CI: [2.11, 41.89]Cochran-Mantel-Haenszel
p-value: 0.820995% CI: [-20.63, 16.19]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population | 37.6 percentage of participants |
| Atezolizumab | Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population | 25.2 percentage of participants |
| Sunitinib | Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population | 33.7 percentage of participants |
p-value: 0.623195% CI: [-10.23, 18.15]Cochran-Mantel-Haenszel
p-value: 0.181695% CI: [-21.86, 5.02]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Time frame: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Crossover population included participants in atezolizumab or sunitinib arms who had crossed over to the atezolizumab and bevacizumab arm. 'Overall Number of Participants Analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population | 24.4 percentage of participants |
| Atezolizumab | Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population | 27.8 percentage of participants |
Secondary
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | 48.0 percentage of participants |
| Atezolizumab | Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | 25.9 percentage of participants |
| Sunitinib | Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | 28.3 percentage of participants |
p-value: 0.019995% CI: [-0.1, 39.44]Cochran-Mantel-Haenszel
p-value: 0.783695% CI: [-20.5, 15.68]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population | 34.7 percentage of participants |
| Atezolizumab | Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population | 23.3 percentage of participants |
| Sunitinib | Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population | 32.7 percentage of participants |
p-value: 0.806895% CI: [-12.04, 16]Cochran-Mantel-Haenszel
p-value: 0.132195% CI: [-22.61, 3.87]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab and Bevacizumab | Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | 46.0 percentage of participants |
| Atezolizumab | Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | 27.8 percentage of participants |
| Sunitinib | Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population | 26.7 percentage of participants |
p-value: 0.014195% CI: [-0.28, 38.94]Cochran-Mantel-Haenszel
p-value: 0.871995% CI: [-17.02, 19.24]Cochran-Mantel-Haenszel
Secondary
PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | 21.7 months |
| Atezolizumab | PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | 10.9 months |
| Sunitinib | PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population | 8.4 months |
p-value: 0.002195% CI: [0.25, 0.75]Log Rank
p-value: 0.656695% CI: [0.56, 1.44]Log Rank
Secondary
PFS Per Modified RECIST Via Investigator Assessment in ITT Population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | PFS Per Modified RECIST Via Investigator Assessment in ITT Population | 16.7 months |
| Atezolizumab | PFS Per Modified RECIST Via Investigator Assessment in ITT Population | 10.9 months |
| Sunitinib | PFS Per Modified RECIST Via Investigator Assessment in ITT Population | 9.9 months |
p-value: 0.086395% CI: [0.5, 1.05]Log Rank
p-value: 0.592295% CI: [0.77, 1.57]Log Rank
Secondary
PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Crossover population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population | 12.6 months |
| Atezolizumab | PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population | 8.3 months |
Secondary
PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: IC1/2/3 population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | 11.1 months |
| Atezolizumab | PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | 5.5 months |
| Sunitinib | PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population | 7.0 months |
p-value: 0.035195% CI: [0.37, 0.97]Log Rank
p-value: 0.976995% CI: [0.64, 1.54]Log Rank
Secondary
PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population | 11.1 months |
| Atezolizumab | PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population | 5.5 months |
| Sunitinib | PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population | 7.8 months |
p-value: 0.254195% CI: [0.59, 1.15]Log Rank
p-value: 0.310395% CI: [0.86, 1.63]Log Rank
Secondary
PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Biomarker evaluable population. Participants with higher than median expression of an immune gene signature were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 16.6 months |
| Atezolizumab | PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 5.5 months |
| Sunitinib | PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 6.8 months |
p-value: 0.008695% CI: [0.28, 0.84]Log Rank
p-value: 0.767595% CI: [0.56, 1.53]Log Rank
Secondary
PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 11.1 months |
| Atezolizumab | PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 5.5 months |
| Sunitinib | PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 7.1 months |
p-value: 0.08395% CI: [0.43, 1.06]Log Rank
p-value: 0.714195% CI: [0.7, 1.69]Log Rank
Secondary
PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Biomarker evaluable population. Participants with higher than median expression of an immune gene signature were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 17.5 months |
| Atezolizumab | PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 5.7 months |
| Sunitinib | PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature | 7.1 months |
p-value: 0.015395% CI: [0.26, 0.87]Log Rank
p-value: 0.554595% CI: [0.48, 1.46]Log Rank
Secondary
PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Population: Biomarker evaluable population. Participants with higher than the 33rd percentile expression of an immune gene signature were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab and Bevacizumab | PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 13.8 months |
| Atezolizumab | PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 5.7 months |
| Sunitinib | PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature | 8.2 months |
p-value: 0.197395% CI: [0.44, 1.18]Log Rank
p-value: 0.773895% CI: [0.65, 1.76]Log Rank
Other Pre-specified
EuroQoL 5 Dimension (EQ-5D) Questionnaire Score
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Time frame: Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)
Population: As this outcome was pre-specified as an exploratory outcome, no results are reported.