Trial Outcomes & Findings for Trial of Vinflunine Plus Capecitabine in Advanced Breast Cancer (NCT NCT01095003)

Last Updated: 2022-04-28

Results Overview

PFS is defined as time from date of randomization to date of the first documentation of objective tumor progression (according to the Independent Response Review Committee (IRC) and based on RECIST version 1.1) or death due to any cause. The PFS was primarily analysed in the Intent-to-treat (ITT) population. Patients lost to follow-up, or without a known record of progression or death at time of analysis had the progression-free survival censored at the date of last tumour assessment or the date of last contact of a follow-up showing no progression, whichever occurs last.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

770 participants

Primary outcome timeframe

Baseline up to 2 years 7 months

Results posted on

2022-04-28

Participant Flow

Participant milestones

Participant milestones
Measure	Vinflunine Plus Capecitabine Vinflunine plus Capecitabine: Vinflunine 280mg/m² as a 20-minute i.v. infusion on day 1 of each cycle repeated every 3 weeks Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks	Capecitabine Single-agent Capecitabine: Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks
Overall Study STARTED	384	386
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	384	386

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial of Vinflunine Plus Capecitabine in Advanced Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Capecitabine Single-agent n=386 Participants Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks	Vinflunine Plus Capecitabine n=384 Participants Vinflunine plus Capecitabine: Vinflunine 280mg/m² as a 20-minute i.v. infusion on day 1 of each cycle repeated every 3 weeks Capecitabine: Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks	Total n=770 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	340 Participants n=5 Participants	329 Participants n=7 Participants	669 Participants n=5 Participants
Age, Categorical >=65 years	46 Participants n=5 Participants	55 Participants n=7 Participants	101 Participants n=5 Participants
Sex: Female, Male Female	386 Participants n=5 Participants	384 Participants n=7 Participants	770 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 2 years 7 months

Population: ITT population

Outcome measures

Outcome measures
Measure	Vinflunine Plus Capecitabine n=384 Participants Vinflunine plus Capecitabine: Vinflunine 280mg/m² as a 20-minute i.v. infusion on day 1 of each cycle repeated every 3 weeks Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks	Capecitabine Single-agent n=386 Participants Capecitabine: Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks
Progression Free Survival	5.6 Months Interval 5.3 to 6.3	4.3 Months Interval 4.1 to 5.6

SECONDARY outcome

Timeframe: Baseline upto 3 years 10 months

Population: ITT population

The overall survival (OS) was defined as the duration between the date of randomisation and the date of death from any cause. The OS analysis was performed in the ITT population and the eligible and per protocol populations once the required number of events (631 deaths) was observed Patients lost to follow-up, or without a known record of death at time of analysis had the OS censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Vinflunine Plus Capecitabine n=384 Participants Vinflunine plus Capecitabine: Vinflunine 280mg/m² as a 20-minute i.v. infusion on day 1 of each cycle repeated every 3 weeks Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks	Capecitabine Single-agent n=386 Participants Capecitabine: Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks
Overall Survival	13.9 Months Interval 11.9 to 15.0	11.7 Months Interval 10.8 to 13.5

SECONDARY outcome

Timeframe: Baseline upto 2 years 7 months

Population: ITT population

ORR defined as documentation of complete or partial response that was subsequently confirmed to first documentation of disease progression or to death due to any cause, whichever occurred first.

Outcome measures

Outcome measures
Measure	Vinflunine Plus Capecitabine n=384 Participants Vinflunine plus Capecitabine: Vinflunine 280mg/m² as a 20-minute i.v. infusion on day 1 of each cycle repeated every 3 weeks Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks	Capecitabine Single-agent n=386 Participants Capecitabine: Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks
Overall Response Rate (ORR)	22.9 Percent Interval 18.8 to 27.5	17.9 Percent Interval 14.2 to 22.1

SECONDARY outcome

Timeframe: Baseline up to 2 years 7 months

Population: ITT population

Disease control rate defined (DCR) as the sum of confirmed complete response, confirmed partial response and stabilisation rate.

Outcome measures

Outcome measures
Measure	Vinflunine Plus Capecitabine n=384 Participants Vinflunine plus Capecitabine: Vinflunine 280mg/m² as a 20-minute i.v. infusion on day 1 of each cycle repeated every 3 weeks Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks	Capecitabine Single-agent n=386 Participants Capecitabine: Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks
Disease Control Rate	57.3 Percent Interval 52.2 to 62.3	47.9 Percent Interval 42.9 to 53.0

SECONDARY outcome

Timeframe: Baseline up to 2 years 7 months

Population: ITT

Measured from the first time that measurement criteria were first met for objective response (documented CR or PR) until recurrence/progression or death whatever the cause.

Outcome measures

Outcome measures
Measure	Vinflunine Plus Capecitabine n=384 Participants Vinflunine plus Capecitabine: Vinflunine 280mg/m² as a 20-minute i.v. infusion on day 1 of each cycle repeated every 3 weeks Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks	Capecitabine Single-agent n=386 Participants Capecitabine: Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks
Duration of Response	57.3 Months Interval 52.2 to 62.3	47.9 Months Interval 42.9 to 53.0

Adverse Events

Vinflunine Plus Capecitabine

Serious events: 107 serious events

Other events: 257 other events

Deaths: 345 deaths

Capecitabine Single-agent

Serious events: 85 serious events

Other events: 262 other events

Deaths: 348 deaths

Serious adverse events

Other adverse events

Additional Information

Karim Keddad

Institut de Recherche Pierre Fabre

Phone: +33.5.34.50.61.69

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Vinflunine Plus Capecitabine n=383 participants at risk Vinflunine plus Capecitabine: Vinflunine 280mg/m² as a 20-minute i.v. infusion on day 1 of each cycle repeated every 3 weeks Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks	Capecitabine Single-agent n=383 participants at risk Capecitabine: Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks
Gastrointestinal disorders Abdominal distension	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Abdominal pain	1.6% 6/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.78% 3/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Abdominal pain upper	1.0% 4/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Colitis	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Constipation	2.3% 9/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Diarrhoea	1.0% 4/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	1.6% 6/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Gastritis	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Ileus paralytic	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Intestinal obstruction	1.6% 6/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Nausea	0.78% 3/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Reflux gastric	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Stomatitis	1.0% 4/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Subileus	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Vomiting	1.6% 6/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Blood and lymphatic system disorders Anaemia	1.0% 4/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.78% 3/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Blood and lymphatic system disorders Febrile neutropenia	1.8% 7/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.52% 2/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Blood and lymphatic system disorders Haemoytique anaemia	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Blood and lymphatic system disorders Leukopenia	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Blood and lymphatic system disorders Neutropenia	1.6% 6/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Blood and lymphatic system disorders Thrombocytopenia	0.52% 2/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Cardiac disorders Anginal pectoris	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Cardiac disorders Cardiomyopathy	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Ear and labyrinth disorders Ear pain	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Asthenia	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Chest pain	0.78% 3/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Condition aggravated	0.52% 2/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	1.6% 6/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Death	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.52% 2/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Fatigue	0.52% 2/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Injection site extravasation	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Mucosal inflammation	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Multi organ failure	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Pain	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Pyrexia	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Sudden death	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.52% 2/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Hepatobiliary disorders Cholecytitis	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Hepatobiliary disorders Cholecystetis acute	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Hepatobiliary disorders Hepatic pain	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Hepatobiliary disorders Hyperbilirubinemai	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.78% 3/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Immune system disorders Hypersensitivity	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Infections and infestations Cellulitis	0.26% 1/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.

Other adverse events
Measure	Vinflunine Plus Capecitabine n=383 participants at risk Vinflunine plus Capecitabine: Vinflunine 280mg/m² as a 20-minute i.v. infusion on day 1 of each cycle repeated every 3 weeks Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks	Capecitabine Single-agent n=383 participants at risk Capecitabine: Capecitabine 825mg/m² per os twice per day for 14 consecutive days starting day 1 of each cycle repeated every 3 weeks
Blood and lymphatic system disorders Neutropenia	19.1% 73/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	8.4% 32/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Cardiac disorders Cardiac disorders	7.3% 28/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	5.7% 22/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Eye disorders Eye disorders	6.0% 23/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	8.1% 31/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Abdominal pain	31.1% 119/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	20.4% 78/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Abdominal pain upper	12.8% 49/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	5.5% 21/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Constipation	28.2% 108/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	7.8% 30/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Diarrhoea	22.5% 86/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	30.3% 116/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Nausea	32.1% 123/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	25.3% 97/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Stomatitis	23.0% 88/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	10.7% 41/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Gastrointestinal disorders Vomiting	27.7% 106/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	16.2% 62/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Asthenia	17.2% 66/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	10.2% 39/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Fatigue	29.0% 111/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	24.0% 92/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Injection site reaction	16.4% 63/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.00% 0/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Oedema peripheral	5.5% 21/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	5.7% 22/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
General disorders Pyrexia	12.0% 46/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	9.1% 35/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Hepatobiliary disorders Hepatobiliary disorders	7.6% 29/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	5.2% 20/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Infections and infestations Infections and infestations	24.8% 95/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	23.5% 90/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Investigations Weight decreased	29.5% 113/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	19.3% 74/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Investigations Weight increased	14.4% 55/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	12.5% 48/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Metabolism and nutrition disorders Anorexia	16.4% 63/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	9.7% 37/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 48/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	3.7% 14/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Musculoskeletal and connective tissue disorders Back pain	5.5% 21/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	6.5% 25/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Musculoskeletal and connective tissue disorders Bone pain	10.2% 39/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	7.8% 30/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.2% 20/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	2.9% 11/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Musculoskeletal and connective tissue disorders Myalgia	9.4% 36/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	1.3% 5/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Musculoskeletal and connective tissue disorders Pain in extremity	9.7% 37/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	6.0% 23/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	8.9% 34/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	8.6% 33/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Nervous system disorders Dizziness	8.6% 33/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	6.0% 23/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Nervous system disorders Headache	15.4% 59/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	9.9% 38/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Nervous system disorders Peripheral sensory neuropathy	8.6% 33/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	5.0% 19/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Psychiatric disorders Insomnia	6.8% 26/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	3.7% 14/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Respiratory, thoracic and mediastinal disorders Cough	10.4% 40/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	8.9% 34/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.6% 52/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	13.3% 51/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Skin and subcutaneous tissue disorders Alopecia	11.0% 42/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	0.78% 3/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Skin and subcutaneous tissue disorders PPES	23.5% 90/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	47.0% 180/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.
Vascular disorders Vascular disorders	15.9% 61/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.	7.3% 28/383 • Adverse events (AEs) are reported from time of first dose of study treatment up to the end of study period (treatment period + follow-up period) up to 5 years 9 months. AEs were collected from treated patients who received at least one dose of study treatment (383 patients in each arm). The same event may appear as both an AE and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another. Specific AE tables were generated separately as per European format.