Trial Outcomes & Findings for ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients (NCT NCT02855944)

NCT ID: NCT02855944

Last Updated: 2023-06-09

Results Overview

The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 349 participants
• Primary outcome timeframe: Assessments every 8 weeks from Cycle 1 Day 1 (C1D1) until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
• Results posted on: 2023-06-09

Participant Flow

A total of 349 patients from 64 sites across 12 countries were enrolled in the initial Treatment Part of the study and randomized to receive rucaparib or chemotherapy. Patients randomized to chemotherapy had the option to cross over to receive rucaparib in the Crossover Part of the study upon progression of disease.

Participant milestones

Measure	Rucaparib Patients randomized to the rucaparib arm received oral rucaparib 600 mg twice a day (BID) in continuous 28-day cycles.	Chemotherapy Patients randomized to the chemotherapy arm received either weekly intravenous (IV) paclitaxel or IV platinum-based chemotherapy per investigator choice and per standard of care. The starting dose of weekly paclitaxel was 60 to 80 mg/m2 administered via IV infusion (ie, on Days 1, 8, and 15) in each 28-day cycle (with a week break from dosing on Day 22 in each cycle). The dosage and administration of single-agent cisplatin or carboplatin or doublet carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine IV infusion followed institutional guidelines for each agent. Upon progression of disease, patients had the option to cross over to rucaparib and receive oral rucaparib 600 mg BID in continuous 28-day cycles.
Period 1: Treatment STARTED	233	116
Period 1: Treatment COMPLETED	218	113
Period 1: Treatment NOT COMPLETED	15	3
Period 2: Crossover to Rucaparib STARTED	0	80
Period 2: Crossover to Rucaparib COMPLETED	0	75
Period 2: Crossover to Rucaparib NOT COMPLETED	0	5

Reasons for withdrawal

Measure	Rucaparib Patients randomized to the rucaparib arm received oral rucaparib 600 mg twice a day (BID) in continuous 28-day cycles.	Chemotherapy Patients randomized to the chemotherapy arm received either weekly intravenous (IV) paclitaxel or IV platinum-based chemotherapy per investigator choice and per standard of care. The starting dose of weekly paclitaxel was 60 to 80 mg/m2 administered via IV infusion (ie, on Days 1, 8, and 15) in each 28-day cycle (with a week break from dosing on Day 22 in each cycle). The dosage and administration of single-agent cisplatin or carboplatin or doublet carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine IV infusion followed institutional guidelines for each agent. Upon progression of disease, patients had the option to cross over to rucaparib and receive oral rucaparib 600 mg BID in continuous 28-day cycles.
Period 1: Treatment Ongoing	14	0
Period 1: Treatment Discontinued prior to starting study drug	1	3
Period 2: Crossover to Rucaparib Ongoing	0	5

Baseline Characteristics

ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients

Baseline characteristics by cohort

Measure	Rucaparib n=233 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=116 Participants Patients randomized to the chemotherapy arm.	Total n=349 Participants Total of all reporting groups
Age, Continuous	58.0 years n=5 Participants	58.5 years n=7 Participants	58.0 years n=5 Participants
Sex: Female, Male Female	233 Participants n=5 Participants	116 Participants n=7 Participants	349 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	219 Participants n=5 Participants	113 Participants n=7 Participants	332 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
ECOG at Baseline ECOG 0	125 Participants n=5 Participants	72 Participants n=7 Participants	197 Participants n=5 Participants
ECOG at Baseline ECOG 1	108 Participants n=5 Participants	44 Participants n=7 Participants	152 Participants n=5 Participants
Number of Prior Chemotherapy Regimens 2	134 Participants n=5 Participants	68 Participants n=7 Participants	202 Participants n=5 Participants
Number of Prior Chemotherapy Regimens 3	58 Participants n=5 Participants	28 Participants n=7 Participants	86 Participants n=5 Participants
Number of Prior Chemotherapy Regimens 4	23 Participants n=5 Participants	11 Participants n=7 Participants	34 Participants n=5 Participants
Number of Prior Chemotherapy Regimens 5	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Number of Prior Chemotherapy Regimens >5	11 Participants n=5 Participants	4 Participants n=7 Participants	15 Participants n=5 Participants
Number of Prior Platinum Regimens 1	12 Participants n=5 Participants	6 Participants n=7 Participants	18 Participants n=5 Participants
Number of Prior Platinum Regimens 2	156 Participants n=5 Participants	74 Participants n=7 Participants	230 Participants n=5 Participants
Number of Prior Platinum Regimens 3	48 Participants n=5 Participants	28 Participants n=7 Participants	76 Participants n=5 Participants
Number of Prior Platinum Regimens 4	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Number of Prior Platinum Regimens 5	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Number of Prior Platinum Regimens >5	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Randomization Stratification: Platinum Status Platinum resistant	120 Participants n=5 Participants	59 Participants n=7 Participants	179 Participants n=5 Participants
Randomization Stratification: Platinum Status Partially platinum-sensitive	65 Participants n=5 Participants	31 Participants n=7 Participants	96 Participants n=5 Participants
Randomization Stratification: Platinum Status Platinum sensitive	48 Participants n=5 Participants	26 Participants n=7 Participants	74 Participants n=5 Participants
Combined Local and Central Lab BRCA Mutation Results BRCA1	181 Participants n=5 Participants	79 Participants n=7 Participants	260 Participants n=5 Participants
Combined Local and Central Lab BRCA Mutation Results BRCA2	52 Participants n=5 Participants	36 Participants n=7 Participants	88 Participants n=5 Participants
Combined Local and Central Lab BRCA Mutation Results Non-BRCA	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Mutation Type Germline	198 Participants n=5 Participants	95 Participants n=7 Participants	293 Participants n=5 Participants
Mutation Type Somatic	35 Participants n=5 Participants	19 Participants n=7 Participants	54 Participants n=5 Participants
Mutation Type Not Available	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Patients with a BRCA Reversion Mutation	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessments every 8 weeks from Cycle 1 Day 1 (C1D1) until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Population: Efficacy Population - All randomized patients in the treatment part of study with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation. As noted in the Baseline Characteristics Module, 1 patient in the Chemotherapy Arm did not have a BRCA mutation (Non-BRCA) and is therefore excluded from the overall number of patients analyzed.

The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure	Rucaparib n=220 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=105 Participants Patients randomized to the chemotherapy arm.
Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (Efficacy Population)	7.4 Months Interval 7.3 to 9.1	5.7 Months Interval 5.5 to 7.3

PRIMARY outcome

Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Population: Intent-to-treat (ITT) Population - All randomized patients in the treatment part of study.

The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure	Rucaparib n=233 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=116 Participants Patients randomized to the chemotherapy arm.
Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (ITT Population)	7.4 Months Interval 6.7 to 7.9	5.7 Months Interval 5.5 to 6.7

SECONDARY outcome

Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Population: Efficacy population with measurable disease at baseline. Efficacy population defined as all randomized patients with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation.

A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

Outcome measures

Measure	Rucaparib n=211 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=96 Participants Patients randomized to the chemotherapy arm.
Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (Efficacy Population)	40.3 percentage of participants Interval 33.6 to 47.2	32.3 percentage of participants Interval 23.1 to 42.6

SECONDARY outcome

Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Population: Intent-to-treat (ITT) population with measurable disease at baseline. ITT population defined as all randomized patients.

A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

Outcome measures

Measure	Rucaparib n=224 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=106 Participants Patients randomized to the chemotherapy arm.
Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (ITT Population)	37.9 percentage of participants Interval 31.6 to 44.7	30.2 percentage of participants Interval 21.7 to 39.9

SECONDARY outcome

Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Population: Efficacy population with measurable disease at baseline and a confirmed response. Efficacy population defined as all randomized patients with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation. As noted in the Baseline Characteristics Module, 1 patient in the Chemotherapy Arm did not have a BRCA mutation (Non-BRCA) and is therefore excluded from the overall number of patients analyzed.

A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure	Rucaparib n=85 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=31 Participants Patients randomized to the chemotherapy arm.
Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (Efficacy Population)	9.4 months Interval 7.5 to 11.1	7.2 months Interval 4.0 to 11.4

SECONDARY outcome

Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Population: Intent-to-treat (ITT) population with measurable disease at baseline and a confirmed response. ITT population defined as all randomized patients.

A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure	Rucaparib n=85 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=32 Participants Patients randomized to the chemotherapy arm.
Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (ITT Population)	9.4 months Interval 7.5 to 11.1	7.2 months Interval 3.9 to 9.4

SECONDARY outcome

Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Population: Efficacy population with measurable disease at baseline and/or CA-125 response evaluable. Efficacy population defined as all randomized patients with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation.

A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or response per Gynecologic Cancer InterGroup Cancer Antigen 125 (GCIG CA-125) criteria. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.

Outcome measures

Measure	Rucaparib n=217 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=101 Participants Patients randomized to the chemotherapy arm.
Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (Efficacy Population)	50.7 percentage of patients Interval 43.8 to 57.5	43.6 percentage of patients Interval 33.7 to 53.8

SECONDARY outcome

Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Population: Intent-to-treat (ITT) population with measurable disease at baseline and/or CA-125 response evaluable. ITT population defined as all randomized patients.

A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or response per Gynecologic Cancer InterGroup Cancer Antigen 125 (GCIG CA-125) criteria. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.

Outcome measures

Measure	Rucaparib n=230 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=111 Participants Patients randomized to the chemotherapy arm.
Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (ITT Population)	47.8 percentage of patients Interval 41.2 to 54.5	40.5 percentage of patients Interval 31.3 to 50.3

SECONDARY outcome

Timeframe: Baseline to the end of Cycle 6, or up to approximately 6 months

Population: Efficacy population - All randomized patients with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation, and with a baseline value and at least one post-baseline value for the EORTC QLQ-C30 Global Health Status score during the first 6 cycles.

EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed.

Outcome measures

Measure	Rucaparib n=197 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=91 Participants Patients randomized to the chemotherapy arm.
Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (Efficacy Population)	0.5 score on a scale Standard Error 0.55	0.3 score on a scale Standard Error 0.86

SECONDARY outcome

Timeframe: Baseline to the end of Cycle 6, or up to approximately 6 months

Population: Intent-to-treat (ITT) population - All randomized patients with a baseline value and at least one post-baseline value for the EORTC QLQ-C30 Global Health Status score during the first 6 cycles.

EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed.

Outcome measures

Measure	Rucaparib n=207 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=101 Participants Patients randomized to the chemotherapy arm.
Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (ITT Population)	0.6 score on a scale Standard Error 0.54	0.4 score on a scale Standard Error 0.82

SECONDARY outcome

Timeframe: All patients were followed for survival up to approximately 3.5 years.

Population: Efficacy Population - All randomized patients in the treatment part of study with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation. As noted in the Baseline Characteristics Module, 1 patient in the Chemotherapy Arm did not have a BRCA mutation (Non-BRCA) and is therefore excluded from the overall number of patients analyzed.

Overall survival (OS) is defined as the number of days from the date of randomization to the date of death (due to any cause). Patients who are still alive were censored on the date of their last available visit or last date known to be alive.

Outcome measures

Measure	Rucaparib n=220 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=105 Participants Patients randomized to the chemotherapy arm.
Overall Survival (Efficacy Population)	21.1 Months Interval 17.9 to 24.9	26.2 Months Interval 22.2 to 29.1

SECONDARY outcome

Timeframe: All patients were followed for survival up to approximately 3.5 years.

Population: Intent-to-Treat (ITT) Population - All randomized patients in the treatment part of the study.

Overall survival (OS) is defined as the number of days from the date of randomization to the date of death (due to any cause). Patients who are still alive were censored on the date of their last available visit or last date known to be alive.

Outcome measures

Measure	Rucaparib n=233 Participants Patients randomized to the rucaparib arm.	Chemotherapy n=116 Participants Patients randomized to the chemotherapy arm.
Overall Survival (ITT Population)	19.4 Months Interval 15.2 to 23.6	25.4 Months Interval 21.4 to 27.6

Adverse Events

Rucaparib (Treatment Part)

Serious events: 66 serious events

Other events: 229 other events

Deaths: 16 deaths

Chemotherapy (Treatment Part)

Serious events: 14 serious events

Other events: 109 other events

Deaths: 4 deaths

Rucaparib (Crossover Part)

Serious events: 24 serious events

Other events: 76 other events

Deaths: 3 deaths

Serious adverse events

Measure	Rucaparib (Treatment Part) n=232 participants at risk Patients randomized to the rucaparib arm in the Treatment Part of the study.	Chemotherapy (Treatment Part) n=113 participants at risk Patients randomized to the chemotherapy arm in the Treatment Part of the study.	Rucaparib (Crossover Part) n=80 participants at risk Patients randomized to chemotherapy who then crossed over upon disease progression and were treated with rucaparib.
Blood and lymphatic system disorders Anemia	7.8% 18/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.8% 2/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	8.8% 7/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Blood and lymphatic system disorders Febrile neutropenia	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Blood and lymphatic system disorders Leukopenia	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Blood and lymphatic system disorders Neutropenia	1.7% 4/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Blood and lymphatic system disorders Thrombocytopenia	2.2% 5/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Cardiac disorders Cardiac disorder	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Cardiac disorders Pericardial effusion	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Abdominal distension	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Abdominal pain	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Ascites	0.86% 2/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Constipation	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Diarrhoea	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Dolichocolon acquired	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Haematemesis	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Ileus	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Intestinal obstruction	2.6% 6/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Large intestine perforation	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Megacolon	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Nausea	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Pancreatitis	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Peritoneal adhesions	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Small intestine obstruction	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Subileus	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Vomiting	1.7% 4/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
General disorders Death	0.86% 2/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
General disorders General physical health deterioration	0.86% 2/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
General disorders Incarcerated hernia	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
General disorders Pyrexia	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Immune system disorders Drug hypersensitivity	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Abdominal infection	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Cellulitis	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Colonic abscess	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Cytomegalovirus colitis	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Device related infection	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Lower respiratory tract infection	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Neutropenic sepsis	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Osteomyelitis	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Pneumonia	1.7% 4/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Sepsis	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.5% 2/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Septic shock	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Urinary tract infection	0.86% 2/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Injury, poisoning and procedural complications Post procedural fever	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Injury, poisoning and procedural complications Radius fracture	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Injury, poisoning and procedural complications Seroma	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Injury, poisoning and procedural complications Tibia fracture	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Alanine aminotransferase increased	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Blood alkaline phosphatase increased	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Blood creatinine increased	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Platelet count decreased	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Cachexia	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Dehydration	0.86% 2/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Hypomagnesaemia	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Hyponatraemia	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	2.6% 6/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.7% 3/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	1.3% 3/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Cerebrovascular accident	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Depressed level of consciousness	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Ischaemic stroke	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Sciatica	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Seizure	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Transient ischaemic attack	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Renal and urinary disorders Acute kidney injury	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Renal and urinary disorders Renal failure	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Reproductive system and breast disorders Fibrocystic breast disease	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Vascular disorders Deep vein thrombosis	1.3% 3/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Blood and lymphatic system disorders Blood disorder	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Blood and lymphatic system disorders Lymphatic disorder	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Cardiac disorders Myocardial infarction	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations COVID-19	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Meningoencephalitis herpatic	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Pneumonia aspiration	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Vascular disorders Arterial occlusive disease	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.

Other adverse events

Measure	Rucaparib (Treatment Part) n=232 participants at risk Patients randomized to the rucaparib arm in the Treatment Part of the study.	Chemotherapy (Treatment Part) n=113 participants at risk Patients randomized to the chemotherapy arm in the Treatment Part of the study.	Rucaparib (Crossover Part) n=80 participants at risk Patients randomized to chemotherapy who then crossed over upon disease progression and were treated with rucaparib.
Blood and lymphatic system disorders Anaemia	56.0% 130/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	31.9% 36/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	46.2% 37/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Blood and lymphatic system disorders Leukopenia	10.3% 24/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	17.7% 20/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	16.2% 13/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Blood and lymphatic system disorders Neutropenia	21.1% 49/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	26.5% 30/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	20.0% 16/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Blood and lymphatic system disorders Thrombocytopenia	21.1% 49/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	14.2% 16/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	17.5% 14/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Cardiac disorders Sinus tachycardia	3.0% 7/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.3% 6/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	3.8% 3/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Abdominal distension	6.9% 16/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	3.5% 4/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 5/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Abdominal pain	24.6% 57/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	17.7% 20/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	21.2% 17/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Abdominal pain upper	9.5% 22/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	4.4% 5/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	10.0% 8/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Ascites	6.0% 14/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.8% 2/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.5% 2/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Constipation	16.8% 39/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	16.8% 19/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	18.8% 15/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Diarrhoea	22.0% 51/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	21.2% 24/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	17.5% 14/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Dyspepsia	8.2% 19/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 7/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.5% 2/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Intestinal obstruction	5.2% 12/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 5/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Nausea	55.2% 128/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	33.6% 38/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	43.8% 35/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Stomatitis	4.7% 11/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 7/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	3.8% 3/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Vomiting	35.3% 82/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	18.6% 21/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	21.2% 17/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
General disorders Asthenia	29.3% 68/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	23.9% 27/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	16.2% 13/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
General disorders Fatigue	25.9% 60/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	26.5% 30/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	21.2% 17/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
General disorders Oedema peripheral	5.6% 13/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	8.0% 9/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.5% 2/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
General disorders Pyrexia	10.8% 25/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 7/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	3.8% 3/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Upper respiratory tract infection	3.4% 8/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.7% 3/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 5/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Infections and infestations Urinary tract infection	9.1% 21/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	4.4% 5/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 5/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Alanine aminotransferase increased	34.1% 79/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	10.6% 12/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	45.0% 36/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Aspartate aminotransferase increased	32.3% 75/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	7.1% 8/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	37.5% 30/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Blood alkaline phosphatase increased	8.2% 19/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.7% 3/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	12.5% 10/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Blood bilirubin increased	9.5% 22/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	10.0% 8/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Blood cholesterol increased	4.3% 10/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 7/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	10.0% 8/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Blood creatinine increased	17.2% 40/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	8.8% 10/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	22.5% 18/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Blood urea increased	4.7% 11/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	4.4% 5/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	10.0% 8/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Electrocardiogram QT prolonged	2.6% 6/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.3% 6/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	7.5% 6/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Electrocardiogram repolarisation abnormality	1.3% 3/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	4.4% 5/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Neutrophil count decreased	2.2% 5/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 7/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.5% 2/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Weight decreased	12.9% 30/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	3.5% 4/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	8.8% 7/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Decreased appetite	20.7% 48/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	17.7% 20/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	27.5% 22/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Hypercholesterolaemia	3.9% 9/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	4.4% 5/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	8.8% 7/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Hyperglycaemia	7.8% 18/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	13.3% 15/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	7.5% 6/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Hypertriglyceridaemia	4.3% 10/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 7/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	8.8% 7/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Hypomagnesaemia	6.0% 14/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.8% 2/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.5% 2/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Musculoskeletal and connective tissue disorders Arthralgia	7.3% 17/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	7.1% 8/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 5/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Musculoskeletal and connective tissue disorders Back pain	5.2% 12/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	4.4% 5/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	11.2% 9/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	4.3% 10/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	3.5% 4/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Dizziness	5.6% 13/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	8.0% 9/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Dysgeusia	16.8% 39/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	7.1% 8/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	13.8% 11/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Headache	7.8% 18/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.3% 6/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	3.8% 3/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Neuropathy peripheral	0.86% 2/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	15.0% 17/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.5% 2/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Neurotoxicity	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	7.1% 8/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.5% 2/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Nervous system disorders Paraesthesia	2.2% 5/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	8.8% 10/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.2% 1/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Psychiatric disorders Insomnia	9.1% 21/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 7/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Respiratory, thoracic and mediastinal disorders Cough	9.1% 21/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	8.0% 9/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	10.0% 8/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.1% 28/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	8.0% 9/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	11.2% 9/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Skin and subcutaneous tissue disorders Alopecia	5.2% 12/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	35.4% 40/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.5% 2/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Skin and subcutaneous tissue disorders Photosensitivity reaction	4.3% 10/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 5/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Skin and subcutaneous tissue disorders Pruritus	4.7% 11/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.7% 3/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	10.0% 8/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Skin and subcutaneous tissue disorders Rash	5.6% 13/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	3.5% 4/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Vascular disorders Hypertension	3.4% 8/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 7/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 5/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Blood and lymphatic system disorders Lymphopenia	4.3% 10/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 7/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 5/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Gastrointestinal disorders Abdominal pain lower	5.6% 13/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.8% 2/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Skin and subcutaneous tissue disorders Erythema	1.7% 4/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	1.8% 2/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	8.8% 7/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Cardiac disorders Sinus bradycardia	1.3% 3/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	3.5% 4/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
General disorders Mucosal inflammation	3.0% 7/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Hepatobiliary disorders Hypertransaminasaemia	3.9% 9/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Blood triglycerides increased	2.6% 6/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	4.4% 5/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Creatinine renal clearance decreased	4.7% 11/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	2.7% 3/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 5/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Gamma-glutamyltransferase increased	3.4% 8/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	6.2% 5/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Platelet count decreased	4.7% 11/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.88% 1/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Investigations Weight increased	0.00% 0/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	4.4% 5/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Hypercreatininaemia	0.43% 1/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Metabolism and nutrition disorders Hypokalaemia	4.3% 10/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	3.5% 4/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
Musculoskeletal and connective tissue disorders Muscle spasms	3.0% 7/232 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	0.00% 0/113 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.	5.0% 4/80 • Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years. Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.

Additional Information

Medical Information Department

Clovis Oncology, Inc.

Phone: +1 415 409 7220

Email: medinfo@clovisoncology.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor's agreements with investigators require proposed public disclosures of trial results to be submitted to Sponsor for review prior to publication. Sponsor may request deletion of confidential information or a delay in publication to address intellectual property concerns, but Sponsor may not suppress publication of the trial results indefinitely. Sponsor may request delay of a single-center publication until after the release of a multi-site publication or an agreed upon period of time.
• Publication restrictions are in place

Restriction type: OTHER