Trial Outcomes & Findings for A Study of Atezolizumab in Combination With Bevacizumab in Spanish Patients With Unresectable or Unsuitable for Locoregional Treatments Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy (NCT NCT04732286)

Last Updated: 2025-05-08

Results Overview

AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The severity of AEs was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) with the following grades: Grade 1 = asymptomatic or mild symptoms; Grade 2 = minimal, local, or non-invasive intervention indicated; Grade 3 = severe or medically significant, but not immediately life-threatening; Grade 4 = life-threatening consequences or urgent intervention indicated and Grade 5 = death related to AE.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

100 participants

Primary outcome timeframe

From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months)

Results posted on

2025-05-08

Participant Flow

A total of 100 participants took part in the study in Spain from 04 May 2021 to 26 April 2024.

Participants with unresectable hepatocellular carcinoma (HCC) who received no prior systemic treatment and were considered unsuitable for locoregional therapy were enrolled in this study to receive a combination of atezolizumab plus bevacizumab until unacceptable toxicity or loss of clinical benefit.

Participant milestones

Participant milestones
Measure	Atezolizumab + Bevacizumab Participants received atezolizumab, 1200 milligrams (mg), intravenously (IV), every 3 weeks (Q3W) along with bevacizumab, 15 milligrams per kilogram (mg/kg), IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Overall Study STARTED	100
Overall Study Intent-to-treat Population (ITT)	99
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	100

Reasons for withdrawal

Reasons for withdrawal
Measure	Atezolizumab + Bevacizumab Participants received atezolizumab, 1200 milligrams (mg), intravenously (IV), every 3 weeks (Q3W) along with bevacizumab, 15 milligrams per kilogram (mg/kg), IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Overall Study Progressive Disease	2
Overall Study Physician Decision	1
Overall Study Study Terminated by Sponsor	31
Overall Study Withdrawal by Subject	10
Overall Study Non-compliance With Study Drug	1
Overall Study Lost to Follow-up	4
Overall Study Death	51

Baseline Characteristics

A Study of Atezolizumab in Combination With Bevacizumab in Spanish Patients With Unresectable or Unsuitable for Locoregional Treatments Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atezolizumab + Bevacizumab n=100 Participants Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Age, Continuous	65.4 years STANDARD_DEVIATION 8.2 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	87 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	73 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	99 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months)

Population: Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.

Outcome measures

Outcome measures
Measure	Atezolizumab + Bevacizumab n=100 Participants Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Number of Participants Who Discontinued Atezolizumab and/or Bevacizumab Due to Adverse Events (AE) of Grade ≥ 3	19 Participants

SECONDARY outcome

Timeframe: Up to 35 months

Population: ITT population included all screened participants (participants who signed the informed consent) who were eligible for the study.

OS was defined as the time from initiation of study treatment to death from any cause. OS was analyzed using Kaplan-Meier (K-M) methods and Greenwood's formula. Any participant who did not die during the study was censored at the last known date to be alive.

Outcome measures

Outcome measures
Measure	Atezolizumab + Bevacizumab n=99 Participants Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Overall Survival (OS)	24.8 months Interval 18.55 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to 35 months

Population: ITT population included all screened participants (participants who signed the informed consent) who were eligible for the study.

PFS was defined as the time from initiation of study treatment to the first occurrence of disease progression (PD) or death from any cause (whichever occurs first), as determined by the investigator according to Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm). PFS was analyzed using K-M methods and Greenwood's formula. Any participant who did not experience disease progression or death during the study and were censored at the last known date to be alive or without disease progression.

Outcome measures

Outcome measures
Measure	Atezolizumab + Bevacizumab n=99 Participants Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Progression-free Survival (PFS)	9.3 months Interval 7.01 to 12.4

SECONDARY outcome

Timeframe: Up to 35 months

Population: ITT population included all screened participants (participants who signed the informed consent) who were eligible for the study.

ORR = percentage of participants with a complete or partial response (CR or PR), on 2 consecutive investigator assessments ≥ 4 weeks apart in participants with measurable disease at baseline as determined by the investigator according to RECIST v1.1. CR = disappearance of all target lesions and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR = at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants without a post-baseline tumor assessment were considered non-responders. 95% confidence interval (CI) was derived using Wilson score intervals. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Atezolizumab + Bevacizumab n=99 Participants Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Objective Response Rate (ORR)	24.2 percentage of participants Interval 16.9 to 33.5

SECONDARY outcome

Timeframe: Up to 35 months

Population: ITT population included all screened participants (participants who signed the informed consent) who were eligible for the study.

TTP was defined as the time from initiation of study treatment to the first occurrence of PD, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, SOD must also demonstrate an absolute increase of ≥ 5 mm. TTP was analyzed using K-M methods and Greenwood's formula. Any participant who had no disease progression was censored at the last known date without disease progression.

Outcome measures

Outcome measures
Measure	Atezolizumab + Bevacizumab n=99 Participants Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Time to Progression (TTP)	11.2 months Interval 8.3 to 13.59

SECONDARY outcome

Timeframe: Up to 35 months

Population: ITT population included all screened participants (participants who signed the informed consent) who were eligible for the study. Overall number analyzed is the number of participants with an overall response of CR or PR.

DOR was defined as the time from the first occurrence of a documented objective response (CR or PR) to PD or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target lesions and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. DOR was analyzed using K-M methods and Greenwood's formula. Any participant who did not experience disease progression or death during the study was censored at the last known date to be alive or without disease progression.

Outcome measures

Outcome measures
Measure	Atezolizumab + Bevacizumab n=24 Participants Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Duration of Response (DOR)	15.9 months Interval 7.87 to 23.74

SECONDARY outcome

Timeframe: Up to 35 months

Population: ITT population included all screened participants (participants who signed the informed consent) who were eligible for the study.

Participants who started second-line of treatment were assessed. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Atezolizumab + Bevacizumab n=99 Participants Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Percentage of Participants Who Started Second-line Treatment	24.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Cycle 42 (1 cycle = 21 days)

Population: Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.

The INR is a standardized measure of the prothrombin time. Blood samples were collected from participants to evaluate coagulation parameters.

Outcome measures

Outcome measures
Measure	Atezolizumab + Bevacizumab n=99 Participants Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Change From Baseline in International Normalized Ratio (INR) Baseline	1.1 INR of prothrombin time Standard Deviation 0.1
Change From Baseline in International Normalized Ratio (INR) Cycle 42	0.1 INR of prothrombin time Standard Deviation 0.0

SECONDARY outcome

Timeframe: Baseline up to Cycle 42 (1 cycle = 21 days)

Population: Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment. Number analyzed is the number of participants with data available for analyses at the specified timepoints.

Blood samples were collected from participants to evaluate of ALBI grades. ALBI assessment grades of 1 to 3 was based on ALBI score calculation. ALBI score= log10 bilirubin (micromole per liter) \[μmol/L\] × 0.66 + albumin (grams per liter) \[g/L\] × -0.0852. ALBI score ≤ -2.60 = ALBI grade 1; -2.60 \< ALBI score ≤ -1.39 = ALBI grade 2 and -1.39 \< ALBI score = ALBI grade 3.

Outcome measures

Outcome measures
Measure	Atezolizumab + Bevacizumab n=100 Participants Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Change From Baseline in Albumin-Bilirubin (ALBI) Score Baseline	-2.7 score Standard Deviation 0.4
Change From Baseline in Albumin-Bilirubin (ALBI) Score Cycle 42	0.4 score Standard Deviation 0.4

SECONDARY outcome

Timeframe: Up to approximately 32 months

Population: Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.

Deterioration of hepatic function was monitored by presence of ascites and/or hepatic encephalopathy.

Outcome measures

Outcome measures
Measure	Atezolizumab + Bevacizumab n=100 Participants Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Percentage of Participants With Ascites and/or Hepatic Encephalopathy	17 percentage of participants

Adverse Events

Atezolizumab + Bevacizumab:

Serious events: 46 serious events

Other events: 98 other events

Deaths: 51 deaths

Serious adverse events

Serious adverse events
Measure	Atezolizumab + Bevacizumab: n=100 participants at risk Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Gastrointestinal disorders Diarrhoea	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Hepatobiliary disorders Hepatitis	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Hepatobiliary disorders Hepatic Function Abnormal	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Endocrine disorders Immune-Mediated Hypothyroidism	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
General disorders Pyrexia	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour Associated Fever	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Duodenal Ulcer Haemorrhage	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Gastric Perforation	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Intestinal Perforation	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Intra-Abdominal Haemorrhage	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Oesophageal Varices Haemorrhage	3.0% 3/100 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Investigations Hepatic Enzyme Increased	1.0% 1/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Nervous system disorders Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Renal and urinary disorders Tubulointerstitial Nephritis	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Ascites	3.0% 3/100 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Abdominal Pain	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Gastrointestinal Haemorrhage	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Upper Gastrointestinal Haemorrhage	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Haemoperitoneum	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Haemorrhoidal Haemorrhage	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Intestinal Obstruction	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Pneumonia	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Pneumonia Pneumococcal	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Urinary Tract Infection	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Abdominal Sepsis	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Biliary Sepsis	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Covid-19	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Covid-19 Pneumonia	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Cellulitis	1.0% 1/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Infective Exacerbation Of Chronic Obstructive Airways Disease	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Peritonsillar Abscess	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Pneumonia Aspiration	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Respiratory Tract Infection	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Spontaneous Bacterial Peritonitis	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Nervous system disorders Hepatic Encephalopathy	5.0% 5/100 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Nervous system disorders Spinal Cord Compression	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Nervous system disorders Encephalopathy	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
General disorders Asthenia	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
General disorders General Physical Health Deterioration	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Injury, poisoning and procedural complications Hip Fracture	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Injury, poisoning and procedural complications Fall	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Injury, poisoning and procedural complications Tibia Fracture	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Injury, poisoning and procedural complications Wound Dehiscence	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Injury, poisoning and procedural complications Wound Evisceration	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Hepatobiliary disorders Cholecystitis Acute	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Hepatobiliary disorders Jaundice	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Investigations Blood Bilirubin Increased	2.0% 2/100 • Number of events 2 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Musculoskeletal and connective tissue disorders Back Pain	3.0% 3/100 • Number of events 3 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Cardiac disorders Atrial Fibrillation	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Cardiac disorders Myocardial Infarction	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Renal and urinary disorders Ureterolithiasis	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Surgical and medical procedures Oesophageal Variceal Ligation	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Surgical and medical procedures Spinal Laminectomy	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Blood and lymphatic system disorders Lymphopenia	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Metabolism and nutrition disorders Dehydration	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Psychiatric disorders Confusional State	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Reproductive system and breast disorders Prostatitis	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Vascular disorders Peripheral Ischaemia	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Vomiting	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Subdiaphragmatic Abscess	1.0% 1/100 • Number of events 1 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.

Other adverse events

Other adverse events
Measure	Atezolizumab + Bevacizumab: n=100 participants at risk Participants received atezolizumab, 1200 mg, IV, Q3W along with bevacizumab, 15 mg/kg, IV, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit.
Gastrointestinal disorders Diarrhoea	30.0% 30/100 • Number of events 64 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Abdominal Pain	22.0% 22/100 • Number of events 32 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Constipation	20.0% 20/100 • Number of events 22 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Vomiting	13.0% 13/100 • Number of events 15 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Abdominal Pain Upper	11.0% 11/100 • Number of events 13 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Nausea	11.0% 11/100 • Number of events 17 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Ascites	9.0% 9/100 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Dry Mouth	6.0% 6/100 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Dyspepsia	6.0% 6/100 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Gastrointestinal disorders Haemorrhoids	5.0% 5/100 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
General disorders Asthenia	46.0% 46/100 • Number of events 78 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
General disorders Pyrexia	13.0% 13/100 • Number of events 16 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
General disorders Oedema Peripheral	11.0% 11/100 • Number of events 16 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
General disorders Mucosal Inflammation	9.0% 9/100 • Number of events 14 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
General disorders Pain	7.0% 7/100 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
General disorders Fatigue	5.0% 5/100 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
General disorders Oedema	5.0% 5/100 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Covid-19	21.0% 21/100 • Number of events 22 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Nasopharyngitis	12.0% 12/100 • Number of events 13 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Infections and infestations Respiratory Tract Infection	7.0% 7/100 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Musculoskeletal and connective tissue disorders Back Pain	14.0% 14/100 • Number of events 17 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Musculoskeletal and connective tissue disorders Myalgia	7.0% 7/100 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	17.0% 17/100 • Number of events 19 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Musculoskeletal and connective tissue disorders Pain In Extremity	7.0% 7/100 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Vascular disorders Hypertension	42.0% 42/100 • Number of events 56 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	24.0% 24/100 • Number of events 29 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Skin and subcutaneous tissue disorders Rash	5.0% 5/100 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Skin and subcutaneous tissue disorders Skin Lesion	5.0% 5/100 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Investigations Blood Bilirubin Increased	9.0% 9/100 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Investigations Lipase Increased	9.0% 9/100 • Number of events 14 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Investigations Platelet Count Decreased	9.0% 9/100 • Number of events 9 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Investigations Amylase Increased	6.0% 6/100 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Investigations Weight Decreased	6.0% 6/100 • Number of events 6 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Investigations Alanine Aminotransferase Increased	5.0% 5/100 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	11.0% 11/100 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.0% 7/100 • Number of events 7 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Respiratory, thoracic and mediastinal disorders Catarrh	5.0% 5/100 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Respiratory, thoracic and mediastinal disorders Productive Cough	5.0% 5/100 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Nervous system disorders Headache	13.0% 13/100 • Number of events 15 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Nervous system disorders Dysgeusia	5.0% 5/100 • Number of events 5 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dysphonia	9.0% 9/100 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Hepatobiliary disorders Hyperbilirubinaemia	10.0% 10/100 • Number of events 13 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Hepatobiliary disorders Hypertransaminasaemia	8.0% 8/100 • Number of events 10 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Renal and urinary disorders Proteinuria	18.0% 18/100 • Number of events 23 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Blood and lymphatic system disorders Thrombocytopenia	11.0% 11/100 • Number of events 18 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Blood and lymphatic system disorders Anaemia	6.0% 6/100 • Number of events 8 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Endocrine disorders Hypothyroidism	14.0% 14/100 • Number of events 14 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Psychiatric disorders Insomnia	10.0% 10/100 • Number of events 11 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.
Metabolism and nutrition disorders Decreased Appetite	22.0% 22/100 • Number of events 31 • AEs and SAEs: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months). All cause mortality: Up to 35 months Safety population included all screened participants (participants who signed the informed consent) who received at least one full or partial dose of study treatment.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigators are free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER