Trial Outcomes & Findings for Testing the Drug Atezolizumab or Placebo With Usual Therapy in First-Line HER2-Positive Metastatic Breast Cancer (NCT NCT03199885)

NCT ID: NCT03199885

Last Updated: 2025-12-30

Results Overview

Will be determined using the current Response Evaluation Criteria in Solid Tumors 1.1 criteria. Analysis will be based on the intent to treat population. The stratified log-rank test will be used to compare the progression free survival between the two treatment arms with the following stratification factors: prior neoadjuvant or adjuvant therapy with trastuzumab (no; yes), estrogen receptor status (positive; negative), disease sites (any visceral without brain metastasis; non-visceral only without brain metastasis; brain metastasis), and choice of taxane (paclitaxel; docetaxel). The Kaplan-Meier estimates will be calculated by treatment arms. Stratified Cox proportional hazards models to estimate the hazard ratio.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

190 participants

Primary outcome timeframe

At the definitive analysis 2.5 years

Results posted on

2025-12-30

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Pertuzumab, Trastuzumab, Taxane Therapy, Placebo) Patients receive pertuzumab IV over 30-60 minutes on days 1 and 22, trastuzumab IV over 30-90 minutes on days 1 and 22, and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 or docetaxel IV over 60 minutes on days 1 and 22. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. Biopsy: Undergo biopsy Bone Scan: Undergo bone scan Computed Tomography: Undergo CT scan Docetaxel: Given IV Magnetic Resonance Imaging: Undergo MRI Paclitaxel: Given IV Pertuzumab: Given IV Placebo Administration: Given IV Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV	Arm II (Pertuzumab, Trastuzumab, Taxane Therapy, Atezolizumab) Patients receive pertuzumab, trastuzumab, and paclitaxel or docetaxel as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. Atezolizumab: Given IV Biopsy: Undergo biopsy Bone Scan: Undergo bone scan Computed Tomography: Undergo CT scan Docetaxel: Given IV Magnetic Resonance Imaging: Undergo MRI Paclitaxel: Given IV Pertuzumab: Given IV Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Overall Study STARTED	93	97
Overall Study COMPLETED	70	72
Overall Study NOT COMPLETED	23	25

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Testing the Drug Atezolizumab or Placebo With Usual Therapy in First-Line HER2-Positive Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Pertuzumab, Trastuzumab, Taxane Therapy, Placebo) n=93 Participants Patients receive pertuzumab IV over 30-60 minutes on days 1 and 22, trastuzumab IV over 30-90 minutes on days 1 and 22, and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 or docetaxel IV over 60 minutes on days 1 and 22. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. Biopsy: Undergo biopsy Bone Scan: Undergo bone scan Computed Tomography: Undergo CT scan Docetaxel: Given IV Magnetic Resonance Imaging: Undergo MRI Paclitaxel: Given IV Pertuzumab: Given IV Placebo Administration: Given IV Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV	Arm II (Pertuzumab, Trastuzumab, Taxane Therapy, Atezolizumab) n=97 Participants Patients receive pertuzumab, trastuzumab, and paclitaxel or docetaxel as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. Atezolizumab: Given IV Biopsy: Undergo biopsy Bone Scan: Undergo bone scan Computed Tomography: Undergo CT scan Docetaxel: Given IV Magnetic Resonance Imaging: Undergo MRI Paclitaxel: Given IV Pertuzumab: Given IV Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV	Total n=190 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=174 Participants	0 Participants n=166 Participants	0 Participants n=167 Participants
Age, Categorical Between 18 and 65 years	74 Participants n=174 Participants	77 Participants n=166 Participants	151 Participants n=167 Participants
Age, Categorical >=65 years	19 Participants n=174 Participants	20 Participants n=166 Participants	39 Participants n=167 Participants
Sex: Female, Male Female	90 Participants n=174 Participants	96 Participants n=166 Participants	186 Participants n=167 Participants
Sex: Female, Male Male	3 Participants n=174 Participants	1 Participants n=166 Participants	4 Participants n=167 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=174 Participants	8 Participants n=166 Participants	21 Participants n=167 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants n=174 Participants	85 Participants n=166 Participants	162 Participants n=167 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=174 Participants	4 Participants n=166 Participants	7 Participants n=167 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=174 Participants	2 Participants n=166 Participants	3 Participants n=167 Participants
Race (NIH/OMB) Asian	3 Participants n=174 Participants	8 Participants n=166 Participants	11 Participants n=167 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=174 Participants	0 Participants n=166 Participants	1 Participants n=167 Participants
Race (NIH/OMB) Black or African American	8 Participants n=174 Participants	11 Participants n=166 Participants	19 Participants n=167 Participants
Race (NIH/OMB) White	76 Participants n=174 Participants	70 Participants n=166 Participants	146 Participants n=167 Participants
Race (NIH/OMB) More than one race	0 Participants n=174 Participants	0 Participants n=166 Participants	0 Participants n=167 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=174 Participants	6 Participants n=166 Participants	10 Participants n=167 Participants

PRIMARY outcome

Timeframe: At the definitive analysis 2.5 years

Outcome measures

Outcome measures
Measure	Arm I (Pertuzumab, Trastuzumab, Taxane Therapy, Placebo) n=93 Participants Patients receive pertuzumab IV over 30-60 minutes on days 1 and 22, trastuzumab IV over 30-90 minutes on days 1 and 22, and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 or docetaxel IV over 60 minutes on days 1 and 22. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. Biopsy: Undergo biopsy Bone Scan: Undergo bone scan Computed Tomography: Undergo CT scan Docetaxel: Given IV Magnetic Resonance Imaging: Undergo MRI Paclitaxel: Given IV Pertuzumab: Given IV Placebo Administration: Given IV Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV	Arm II (Pertuzumab, Trastuzumab, Taxane Therapy, Atezolizumab) n=97 Participants Patients receive pertuzumab, trastuzumab, and paclitaxel or docetaxel as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. Atezolizumab: Given IV Biopsy: Undergo biopsy Bone Scan: Undergo bone scan Computed Tomography: Undergo CT scan Docetaxel: Given IV Magnetic Resonance Imaging: Undergo MRI Paclitaxel: Given IV Pertuzumab: Given IV Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Progression-Free Survival (PFS)	40.5 percentage of participants Interval 29.7 to 51.0	52.3 percentage of participants Interval 41.4 to 62.2

SECONDARY outcome

Timeframe: At definitive analysis-2.5 years

Analysis will be based on the intent to treat population. The stratification factors are the same as what are used in the stratified log-rank test for the primary analysis on progression free survival. The Kaplan-Meier estimates will be calculated by treatment arms. Stratified Cox proportional hazards models to estimate the hazard ratio.

Outcome measures

Outcome measures
Measure	Arm I (Pertuzumab, Trastuzumab, Taxane Therapy, Placebo) n=93 Participants Patients receive pertuzumab IV over 30-60 minutes on days 1 and 22, trastuzumab IV over 30-90 minutes on days 1 and 22, and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 or docetaxel IV over 60 minutes on days 1 and 22. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. Biopsy: Undergo biopsy Bone Scan: Undergo bone scan Computed Tomography: Undergo CT scan Docetaxel: Given IV Magnetic Resonance Imaging: Undergo MRI Paclitaxel: Given IV Pertuzumab: Given IV Placebo Administration: Given IV Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV	Arm II (Pertuzumab, Trastuzumab, Taxane Therapy, Atezolizumab) n=97 Participants Patients receive pertuzumab, trastuzumab, and paclitaxel or docetaxel as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. Atezolizumab: Given IV Biopsy: Undergo biopsy Bone Scan: Undergo bone scan Computed Tomography: Undergo CT scan Docetaxel: Given IV Magnetic Resonance Imaging: Undergo MRI Paclitaxel: Given IV Pertuzumab: Given IV Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Overall Survival (OS)	86.3 percentage of participants Interval 77.5 to 93.0	87.4 percentage of participants Interval 77.1 to 92.1

SECONDARY outcome

Timeframe: 38 months after study activation.

Population: This analysis was restricted to the sub-cohort of patients randomized six months or more prior to May 20, 2022. Only response data collected up to May 20, 2022, were included in this analysis. We used RECIST v1.1. It involves target lesion, nontarget lesion, second primary cancer, and death.

Defined as complete response or partial response. Will be determined using Response Evaluation Criteria in Solid Tumors 1.1 criteria. The stratified Cochran-Mantel-Haenszel test will be used to compare the object response between the treatment arms.

Outcome measures

Outcome measures
Measure	Arm I (Pertuzumab, Trastuzumab, Taxane Therapy, Placebo) n=77 Participants Patients receive pertuzumab IV over 30-60 minutes on days 1 and 22, trastuzumab IV over 30-90 minutes on days 1 and 22, and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 or docetaxel IV over 60 minutes on days 1 and 22. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. Biopsy: Undergo biopsy Bone Scan: Undergo bone scan Computed Tomography: Undergo CT scan Docetaxel: Given IV Magnetic Resonance Imaging: Undergo MRI Paclitaxel: Given IV Pertuzumab: Given IV Placebo Administration: Given IV Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV	Arm II (Pertuzumab, Trastuzumab, Taxane Therapy, Atezolizumab) n=68 Participants Patients receive pertuzumab, trastuzumab, and paclitaxel or docetaxel as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, prior to weeks 10, 19, 28 and then at 9, 12, 15, 18, 21, and 24 months from study entry, every 3 months through year 3, every 6 months for years 4 and 5, and then every 6 months for years 6 through 10 from study entry. Patients undergo a bone scan at baseline, every 6 months from study entry, every 6 months through year 3, and every 12 months for years 4 and 5. Atezolizumab: Given IV Biopsy: Undergo biopsy Bone Scan: Undergo bone scan Computed Tomography: Undergo CT scan Docetaxel: Given IV Magnetic Resonance Imaging: Undergo MRI Paclitaxel: Given IV Pertuzumab: Given IV Quality-of-Life Assessment: Ancillary studies Trastuzumab: Given IV
Overall Objective Response	79.4 percentage of participants Interval 68.4 to 87.3	77.9 percentage of participants Interval 67.5 to 85.7

SECONDARY outcome

Timeframe: Every 6 months up to 8 years

Will be categorized using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0. Comparisons of the adverse events between the two treatment arms will be done by the Fisher's exact test.

Outcome measures

Outcome data not reported

Adverse Events

Arm I (Pertuzumab, Trastuzumab, Taxane Therapy, Placebo)

Serious events: 24 serious events

Other events: 90 other events

Deaths: 17 deaths

Arm II (Pertuzumab, Trastuzumab, Taxane Therapy, Atezolizumab)

Serious events: 27 serious events

Other events: 96 other events

Deaths: 14 deaths

Serious adverse events

Other adverse events

Additional Information

Director, Department of Regulatory Affairs

NRG Oncology

Phone: 412-339-5300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Arm I (Pertuzumab, Trastuzumab, Taxane Therapy, Placebo) n=91 participants at risk Arm I (pertuzumab, trastuzumab, taxane therapy, placebo)	Arm II (Pertuzumab, Trastuzumab, Taxane Therapy, Atezolizumab) n=96 participants at risk Arm II (pertuzumab, trastuzumab, taxane therapy, atezolizumab)
Endocrine disorders Adrenal insufficiency	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Investigations Alanine aminotransferase increased	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	3.1% 3/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Investigations Alkaline phosphatase increased	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Immune system disorders Anaphylaxis	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	0.00% 0/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Blood and lymphatic system disorders Anemia	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	3.1% 3/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Metabolism and nutrition disorders Anorexia	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	0.00% 0/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Musculoskeletal and connective tissue disorders Arthritis	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	0.00% 0/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Investigations Aspartate aminotransferase increased	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	3.1% 3/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Respiratory, thoracic and mediastinal disorders Aspiration	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Cardiac disorders Atrial fibrillation	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Investigations Cardiac troponin T increased	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	0.00% 0/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Infections and infestations Catheter related infection	2.2% 2/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Hepatobiliary disorders Cholecystitis	2.2% 2/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	2.1% 2/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Colitis	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	3.1% 3/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Investigations Creatinine increased	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	2.1% 2/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Metabolism and nutrition disorders Dehydration	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	3.1% 3/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Diarrhea	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	5.2% 5/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Dysphagia	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	0.00% 0/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Esophagitis	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
General disorders Fatigue	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Blood and lymphatic system disorders Febrile neutropenia	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	4.2% 4/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
General disorders Fever	2.2% 2/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	2.1% 2/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Hepatobiliary disorders Gallbladder perforation	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Gastric hemorrhage	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	0.00% 0/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	0.00% 0/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Nervous system disorders Headache	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	0.00% 0/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Cardiac disorders Heart failure	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Hepatobiliary disorders Hepatic failure	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Nervous system disorders Hydrocephalus	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	0.00% 0/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Endocrine disorders Hyperthyroidism	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Metabolism and nutrition disorders Hypokalemia	2.2% 2/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	3.1% 3/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Vascular disorders Hypotension	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	2.1% 2/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.3% 3/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	2.1% 2/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Immune system disorders Immune system disorders - Other, specify	0.00% 0/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	1.0% 1/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Infections and infestations Infections and infestations - Other, specify	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	0.00% 0/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.

Other adverse events
Measure	Arm I (Pertuzumab, Trastuzumab, Taxane Therapy, Placebo) n=91 participants at risk Arm I (pertuzumab, trastuzumab, taxane therapy, placebo)	Arm II (Pertuzumab, Trastuzumab, Taxane Therapy, Atezolizumab) n=96 participants at risk Arm II (pertuzumab, trastuzumab, taxane therapy, atezolizumab)
Gastrointestinal disorders Abdominal pain	19.8% 18/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	15.6% 15/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Endocrine disorders Adrenal insufficiency	9.9% 9/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	10.4% 10/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Investigations Alanine aminotransferase increased	20.9% 19/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	29.2% 28/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Investigations Alkaline phosphatase increased	24.2% 22/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	20.8% 20/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	5.5% 5/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	6.2% 6/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Skin and subcutaneous tissue disorders Alopecia	51.6% 47/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	54.2% 52/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Blood and lymphatic system disorders Anemia	60.4% 55/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	61.5% 59/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Metabolism and nutrition disorders Anorexia	28.6% 26/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	32.3% 31/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Psychiatric disorders Anxiety	12.1% 11/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	7.3% 7/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	25.3% 23/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	13.5% 13/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Investigations Aspartate aminotransferase increased	20.9% 19/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	29.2% 28/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Musculoskeletal and connective tissue disorders Back pain	17.6% 16/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	14.6% 14/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Bloating	6.6% 6/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	2.1% 2/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	5.5% 5/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	10.4% 10/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Investigations Blood bilirubin increased	2.2% 2/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	9.4% 9/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Eye disorders Blurred vision	8.8% 8/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	6.2% 6/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Musculoskeletal and connective tissue disorders Bone pain	5.5% 5/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	5.2% 5/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Reproductive system and breast disorders Breast pain	6.6% 6/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	6.2% 6/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
General disorders Chills	6.6% 6/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	12.5% 12/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Colitis	4.4% 4/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	7.3% 7/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Constipation	33.0% 30/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	31.2% 30/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Respiratory, thoracic and mediastinal disorders Cough	31.9% 29/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	27.1% 26/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Investigations Creatinine increased	11.0% 10/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	17.7% 17/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Metabolism and nutrition disorders Dehydration	5.5% 5/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	14.6% 14/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Psychiatric disorders Depression	12.1% 11/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	7.3% 7/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Diarrhea	79.1% 72/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	85.4% 82/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Nervous system disorders Dizziness	18.7% 17/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	12.5% 12/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Eye disorders Dry eye	9.9% 9/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	4.2% 4/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Dry mouth	6.6% 6/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	8.3% 8/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Skin and subcutaneous tissue disorders Dry skin	17.6% 16/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	16.7% 16/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Nervous system disorders Dysgeusia	20.9% 19/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	24.0% 23/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Dyspepsia	12.1% 11/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	13.5% 13/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Gastrointestinal disorders Dysphagia	1.1% 1/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	5.2% 5/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	20.9% 19/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	20.8% 20/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Renal and urinary disorders Dysuria	7.7% 7/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	3.1% 3/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Respiratory, thoracic and mediastinal disorders Epistaxis	28.6% 26/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	25.0% 24/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Skin and subcutaneous tissue disorders Erythema multiforme	3.3% 3/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	9.4% 9/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Eye disorders Eye disorders - Other, specify	11.0% 10/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	12.5% 12/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
General disorders Fatigue	65.9% 60/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	70.8% 68/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.
Blood and lymphatic system disorders Febrile neutropenia	2.2% 2/91 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.	7.3% 7/96 • 38 months from study activation. Participants at Risk includes any patient who submitted an AE form. Adverse event data were reported by sites on 187 patients. Some patients withdrew consent shortly after randomization and adverse event data were not submitted. However, they were still at risk for mortality prior to consent withdrawal. Therefore we did not have any data on adverse events from 3 BR004 participants. This led to the difference between the number at risk for mortality and number at risk for adverse events.