Trial Outcomes & Findings for CANTATA: CB-839 With Cabozantinib vs. Cabozantinib With Placebo in Patients With Metastatic Renal Cell Carcinoma (NCT NCT03428217)

Last Updated: 2023-03-20

Results Overview

PFS is defined as the time from randomization to the occurrence of disease progression as assessed by the IRC using RECIST v1.1 or death from any cause, whichever occurs first. Subjects not experiencing disease progression or death at the time of analysis of PFS will be censored at the date of the last evaluable radiographic disease assessment. RECIST v1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

444 participants

Primary outcome timeframe

Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.14 months.

Results posted on

2023-03-20

Participant Flow

Eligible participants were randomized in a 1:1 ratio to either the Pbo-Cabo arm or the CB-Cabo arm. Randomization was stratified by prior treatment with PD-1/PD-L1 inhibitor therapy (yes vs. no) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Prognostic Risk Group (favorable vs. intermediate vs. poor).

Participant milestones

Participant milestones
Measure	Pbo-Cabo Placebo twice daily (BID) + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first.	CB-Cabo CB-839 800 mg BID + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.
Overall Study STARTED	223	221
Overall Study Received at Least 1 Dose of Study Drug	221	221
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	223	221

Reasons for withdrawal

Reasons for withdrawal
Measure	Pbo-Cabo Placebo twice daily (BID) + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first.	CB-Cabo CB-839 800 mg BID + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.
Overall Study Death	89	93
Overall Study Withdrawal by Subject	8	7
Overall Study Lost to Follow-up	1	3
Overall Study Study terminated by sponsor	124	118
Overall Study Other, Not Specified	1	0

Baseline Characteristics

CANTATA: CB-839 With Cabozantinib vs. Cabozantinib With Placebo in Patients With Metastatic Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pbo-Cabo n=223 Participants Placebo twice daily (BID) + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first.	CB-Cabo n=221 Participants CB-839 800 mg BID + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.	Total n=444 Participants Total of all reporting groups
Age, Continuous	61.7 years STANDARD_DEVIATION 10.33 • n=5 Participants	60.6 years STANDARD_DEVIATION 10.37 • n=7 Participants	61.2 years STANDARD_DEVIATION 10.36 • n=5 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	47 Participants n=7 Participants	115 Participants n=5 Participants
Sex: Female, Male Male	155 Participants n=5 Participants	174 Participants n=7 Participants	329 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	173 Participants n=5 Participants	176 Participants n=7 Participants	349 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	36 Participants n=5 Participants	34 Participants n=7 Participants	70 Participants n=5 Participants
Race/Ethnicity, Customized White	176 Participants n=5 Participants	174 Participants n=7 Participants	350 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	31 Participants n=5 Participants	32 Participants n=7 Participants	63 Participants n=5 Participants
Race/Ethnicity, Customized Other, Not Specified	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Asian	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Stratification Factor: Prior PD-1/PD-L1 Inhibitor Therapy Yes	139 Participants n=5 Participants	137 Participants n=7 Participants	276 Participants n=5 Participants
Stratification Factor: Prior PD-1/PD-L1 Inhibitor Therapy No	84 Participants n=5 Participants	84 Participants n=7 Participants	168 Participants n=5 Participants
Stratification Factor: IMDC Category Poor	35 Participants n=5 Participants	35 Participants n=7 Participants	70 Participants n=5 Participants
Stratification Factor: IMDC Category Intermediate	149 Participants n=5 Participants	147 Participants n=7 Participants	296 Participants n=5 Participants
Stratification Factor: IMDC Category Favorable	39 Participants n=5 Participants	39 Participants n=7 Participants	78 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.14 months.

Population: Intent-to-Treat (ITT) Analysis Set: All randomized participants, analyzed according to the treatment group to which they are randomized.

Outcome measures

Outcome measures
Measure	Pbo-Cabo n=223 Participants Placebo twice daily (BID) + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first.	CB-Cabo n=221 Participants CB-839 800 mg BID + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.
Progression-Free Survival (PFS) as Assessed by the Independent Radiology Committee (IRC)	9.33 months Interval 7.64 to 11.01	9.17 months Interval 7.59 to 11.1

SECONDARY outcome

Timeframe: Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for OS was 25.86 months.

Population: ITT Analysis Set: All randomized participants, analyzed according to the treatment group to which they are randomized.

OS is defined as the time from randomization to death due to any cause. Estimated from Kaplan-Meier methodology. 95% confidence interval (CI) based on Brookmeyer-Crowley methodology.

Outcome measures

Outcome measures
Measure	Pbo-Cabo n=223 Participants Placebo twice daily (BID) + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first.	CB-Cabo n=221 Participants CB-839 800 mg BID + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.
Overall Survival (OS)	24.84 months Interval 21.59 to Not estimable due to small number of events.	22.24 months Interval 18.56 to Not estimable due to small number of events.

SECONDARY outcome

Timeframe: Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.64 months.

Population: ITT Analysis Set: All randomized participants, analyzed according to the treatment group to which they are randomized.

Outcome measures

Outcome measures
Measure	Pbo-Cabo n=223 Participants Placebo twice daily (BID) + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first.	CB-Cabo n=221 Participants CB-839 800 mg BID + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.
PFS as Assessed by the Investigator	8.38 months Interval 6.34 to 9.79	9.17 months Interval 7.49 to 9.46

Adverse Events

Pbo-Cabo

Serious events: 74 serious events

Other events: 213 other events

Deaths: 89 deaths

CB-Cabo

Serious events: 90 serious events

Other events: 222 other events

Deaths: 93 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Calithera Biosciences, Inc

Phone: 650-870-1000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No publication by the PI before either a multi-site publication or 18 months after final multi-site study report. PI can only publish their own results and provide 45 days in advance notice. PI must delete any Calithera confidential information from the publication other than study results and give good faith consideration to other comments made by Calithera. The PI must delay the publication for up to 45 days if requested by Calithera and publicly acknowledge Calithera and Pfizer support.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Pbo-Cabo n=217 participants at risk Placebo BID + cabozantinib (60 mg QD) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.	CB-Cabo n=225 participants at risk CB-839 800 mg BID + cabozantinib (60 mg QD) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.
Vascular disorders Hypertension	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.89% 2/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Vascular disorders Deep vein thrombosis	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Vascular disorders Embolism	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Vascular disorders Haemorrhage	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Vascular disorders Hypotension	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Vascular disorders Thrombophlebitis	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Vascular disorders Vena cava thrombosis	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Surgical and medical procedures Nerve block	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.89% 2/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to pelvis	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tonsil cancer	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Social circumstances Pregnancy of partner	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders General physical health deterioration	0.92% 2/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Fatigue	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.89% 2/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Asthenia	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Chest pain	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Chills	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Death	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Malaise	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Mucosal inflammation	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Non-cardiac chest pain	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Pyrexia	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Psychiatric disorders Confusional state	0.92% 2/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.89% 2/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Psychiatric disorders Delirium	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Reproductive system and breast disorders Prostatitis	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Injury, poisoning and procedural complications Overdose	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.89% 2/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.89% 2/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Injury, poisoning and procedural complications Fall	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Injury, poisoning and procedural complications Femur fracture	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Injury, poisoning and procedural complications Procedural pain	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Injury, poisoning and procedural complications Traumatic fracture	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.00% 0/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Investigations Troponin I increased	0.00% 0/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.44% 1/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Cardiac disorders Atrial fibrillation	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.89% 2/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Cardiac disorders Myocardial infarction	0.46% 1/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	0.89% 2/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.

Other adverse events
Measure	Pbo-Cabo n=217 participants at risk Placebo BID + cabozantinib (60 mg QD) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.	CB-Cabo n=225 participants at risk CB-839 800 mg BID + cabozantinib (60 mg QD) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.
Vascular disorders Hypertension	33.2% 72/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	36.4% 82/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Vascular disorders Hypotension	6.0% 13/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	4.4% 10/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Fatigue	50.2% 109/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	41.8% 94/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Asthenia	22.6% 49/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	21.8% 49/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Mucosal inflammation	16.6% 36/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	10.2% 23/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Oedema peripheral	9.7% 21/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	9.8% 22/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Pyrexia	6.9% 15/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	8.9% 20/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
General disorders Chest pain	6.0% 13/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	4.0% 9/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Psychiatric disorders Insomnia	7.8% 17/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	9.3% 21/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Psychiatric disorders Anxiety	5.5% 12/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	7.1% 16/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Psychiatric disorders Depression	7.4% 16/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	3.1% 7/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Injury, poisoning and procedural complications Fall	5.5% 12/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	4.9% 11/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Investigations Weight decreased	30.0% 65/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	34.2% 77/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Investigations Alanine aminotransferase increased	18.0% 39/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	28.0% 63/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Investigations Aspartate aminotransferase increased	18.4% 40/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	24.9% 56/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Investigations Blood creatinine increased	5.5% 12/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	10.7% 24/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Investigations Blood alkaline phosphatase increased	6.5% 14/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	6.7% 15/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Respiratory, thoracic and mediastinal disorders Cough	18.9% 41/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	22.2% 50/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Respiratory, thoracic and mediastinal disorders Dysphonia	18.9% 41/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	14.7% 33/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.7% 34/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	13.3% 30/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.4% 16/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	8.9% 20/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.0% 13/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	9.3% 21/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Blood and lymphatic system disorders Anaemia	13.4% 29/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	12.4% 28/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Blood and lymphatic system disorders Thrombocytopenia	6.5% 14/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	8.9% 20/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Nervous system disorders Dysgeusia	24.0% 52/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	18.2% 41/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Nervous system disorders Headache	14.7% 32/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	17.3% 39/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Nervous system disorders Dizziness	11.1% 24/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	10.2% 23/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Nervous system disorders Paraesthesia	5.5% 12/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	4.4% 10/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Eye disorders Vision blurred	6.5% 14/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	9.8% 22/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Eye disorders Photophobia	3.7% 8/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	11.6% 26/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Gastrointestinal disorders Diarrhoea	73.7% 160/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	72.0% 162/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Gastrointestinal disorders Nausea	54.4% 118/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	54.7% 123/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Gastrointestinal disorders Vomiting	34.6% 75/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	34.2% 77/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Gastrointestinal disorders Constipation	29.0% 63/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	30.7% 69/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Gastrointestinal disorders Stomatitis	22.6% 49/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	20.9% 47/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Gastrointestinal disorders Abdominal pain	18.0% 39/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	17.8% 40/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Gastrointestinal disorders Gastrooesophageal reflux disease	11.1% 24/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	18.7% 42/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Gastrointestinal disorders Dyspepsia	12.9% 28/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	15.6% 35/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Gastrointestinal disorders Abdominal pain upper	11.5% 25/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	9.3% 21/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.
Gastrointestinal disorders Dry mouth	9.7% 21/217 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.	6.2% 14/225 • All-cause mortality: for a maximum follow-up period of 25.86 months; Intent to Treat Population. Adverse events: From first dose of study drug through at least 28 days after last dose of all study treatments, or until initiation of a new anticancer therapy (if earlier). Overall median duration of safety follow-up was 280.0 days. Safety Analysis Population (all participants who received any study drug, analyzed according to the actual treatment received; 4 Pbo-Cabo participants received CB-Cabo). Per protocol, Grade 5 disease progression events are excluded from these tables. Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression.