Trial Outcomes & Findings for Trial of Vinflunine Versus Alkylating Agent in Metastatic Breast Cancer (NCT NCT01091168)

Last Updated: 2019-09-16

Results Overview

The main endpoint of this study is overall survival defined as the time from randomisation to the date of death or last follow-up. For patients who have not died, survival duration will be censored at the date of last contact or last follow-up or the date of last news.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

594 participants

Primary outcome timeframe

From baseline up to 3 years 1 month

Results posted on

2019-09-16

Participant Flow

Participant milestones

Participant milestones
Measure	Vinflunine (VFL) Patients randomised in the test arm (arm A) received Vinflunine at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Alkylating Agent Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Overall Study STARTED	298	296
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	298	296

Reasons for withdrawal

Reasons for withdrawal
Measure	Vinflunine (VFL) Patients randomised in the test arm (arm A) received Vinflunine at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Alkylating Agent Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Overall Study Progressive disease	250	234
Overall Study Adverse Event	21	24
Overall Study Lost to Follow-up	0	1
Overall Study Physician, patient's decision, other	27	37

Baseline Characteristics

Trial of Vinflunine Versus Alkylating Agent in Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Vinflunine n=298 Participants Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Arm B: Alkylating Agent of Physician Choice n=296 Participants Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin	Total n=594 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	236 Participants n=5 Participants	227 Participants n=7 Participants	463 Participants n=5 Participants
Age, Categorical >=65 years	62 Participants n=5 Participants	69 Participants n=7 Participants	131 Participants n=5 Participants
Sex: Female, Male Female	298 Participants n=5 Participants	296 Participants n=7 Participants	594 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: From baseline up to 3 years 1 month

Population: ITT population

Outcome measures

Outcome measures
Measure	Vinflunine n=298 Participants Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Alkylating Agent n=296 Participants Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Overall Survival	9.1 Months Interval 7.7 to 10.4	9.3 Months Interval 7.5 to 10.9

SECONDARY outcome

Timeframe: From baseline up to 3 years 1 month

Population: ITT population

DCR was defined as the proportion of patients with Complete Response (CR), Partial Response (PR) and stable disease (SD), relative to the total number of patients in the analysed population.

Outcome measures

Outcome measures
Measure	Vinflunine n=298 Participants Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Alkylating Agent n=296 Participants Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Disease Control Rate (DCR)	43.6 Percentage of participants Interval 37.9 to 49.3	35.5 Percentage of participants Interval 30.0 to 41.2

SECONDARY outcome

Timeframe: From baseline to cut-off date(27 August 2012), up to 3 years

Population: ITT population

PFS was defined as the time from randomisation to the first tumour progression or death due to any cause in the absence of previous documentation of objective tumour progression. PFS was performed in the ITT and eligible populations every 6 weeks based on RECIST version 1.1. For patients lost of follow up, or without a known record of progression or death, PFS was censored at the date of last tumour assessment or the date of last contact of a follow-up showing no progression which ever occured last.

Outcome measures

Outcome measures
Measure	Vinflunine n=298 Participants Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Alkylating Agent n=296 Participants Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Progression Free Survival (PFS)	2.5 Months Interval 1.7 to 2.7	1.9 Months Interval 1.5 to 2.6

Adverse Events

Vinflunine

Serious events: 82 serious events

Other events: 197 other events

Deaths: 276 deaths

Alkylating Agent

Serious events: 66 serious events

Other events: 262 other events

Deaths: 274 deaths

Serious adverse events

Other adverse events

Additional Information

Dr 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 n=297 participants at risk Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Alkylating Agent n=290 participants at risk Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Blood and lymphatic system disorders Neutropenia	2.0% 6/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Blood and lymphatic system disorders Anaemia	2.0% 6/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Blood and lymphatic system disorders Febrile neutropenia	1.0% 3/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Blood and lymphatic system disorders Thrombocytopenia	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.69% 2/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Blood and lymphatic system disorders Endocardititis staphylococcal	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Constipation	1.7% 5/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Vomiting	2.0% 6/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	1.0% 3/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Abdominal pain	1.3% 4/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Ileus	1.0% 3/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Ileus paralytic	1.0% 3/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Stomatis	1.0% 3/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Intestinal obstruction	0.67% 2/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Nausea	0.67% 2/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Haematemesis	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Abdominal pain upper	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Dysphagia	0.00% 0/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Oesophagial stenosis	0.00% 0/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Upper gastrointestinal haemorrage	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
General disorders Asthenia	0.67% 2/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
General disorders Fatigue	0.67% 2/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
General disorders Femur fracture	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Injury, poisoning and procedural complications Humerus fracture	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Injury, poisoning and procedural complications Allergic transfusion reaction	0.00% 0/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Injury, poisoning and procedural complications Fall	0.00% 0/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Investigations Transaminases increased	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Cardiac disorders Arteriospasm coronary	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Cardiac disorders Atrial fibrillation	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Cardiac disorders Cardiac failure	0.00% 0/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	12.8% 38/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	14.8% 43/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Psychiatric disorders Confusional state	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Psychiatric disorders Hallucination	0.00% 0/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.3% 4/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.69% 2/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 6/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.69% 2/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.34% 1/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.34% 1/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.00% 0/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)

Other adverse events
Measure	Vinflunine n=297 participants at risk Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks. vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks	Alkylating Agent n=290 participants at risk Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country. Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Blood and lymphatic system disorders Neutropenia	12.5% 37/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	10.7% 31/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Blood and lymphatic system disorders Thrombocyotopenia	1.0% 3/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	13.4% 39/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Constipation	34.3% 102/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	7.9% 23/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Nausea	23.6% 70/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	23.1% 67/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Abdominal pain	22.2% 66/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	5.5% 16/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Stomatitis	17.5% 52/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	6.2% 18/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Vomiting	11.4% 34/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	11.4% 33/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Gastrointestinal disorders Diarrhoea	5.4% 16/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	6.6% 19/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
General disorders Asthenia	30.0% 89/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	14.8% 43/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
General disorders Injection site reaction	9.8% 29/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	0.69% 2/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
General disorders Fatigue	7.7% 23/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	8.6% 25/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Investigations Weight decreased	8.8% 26/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	5.9% 17/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Nervous system disorders Peripheral sensory neuropathy	7.1% 21/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	1.7% 5/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Musculoskeletal and connective tissue disorders Myalgia	12.8% 38/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	1.7% 5/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 21/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	1.0% 3/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Metabolism and nutrition disorders Anorexia	10.4% 31/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	8.3% 24/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)
Skin and subcutaneous tissue disorders Alopecia	10.1% 30/297 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)	3.1% 9/290 • Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm). The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT \>=1%)