Trial Outcomes & Findings for A Study of Vinflunine Plus Gemcitabine Versus Paclitaxel Plus Gemcitabine in Patients With Advanced Breast Cancer (NCT NCT02054338)

NCT ID: NCT02054338

Last Updated: 2019-08-28

Results Overview

The primary efficacy parameter was Progression-free survival (PFS) analysed in the Intent-to-treat (ITT) population. PFS was defined as the time elapsed from randomisation date until the date of progression or death due to any cause (whichever came first).Tumor response was evaluated using the RECIST version 1.0 every 6 weeks until progression was recorded.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

1004 participants

Primary outcome timeframe

PFS was calculated from the registration date until the date of progression or death due to any cause if no progression was recorded first (median duration of follow-up: 14.1 months)

Results posted on

2019-08-28

Participant Flow

Participant milestones

Participant milestones
Measure	Vinflunine Plus Gemcitabine vinflunine 320 mg/m² D1 plus gemcitabine 1000 mg/m2 D1 and D8 every 3 weeks Vinflunine vinflunine plus gemcitabine: 320 mg/m² IV on day 1 plus gemcitabine 1000 mg/m² on days 1 and 8 of each cycle repeated every 3 weeks	Paclitaxel Plus Gemcitabine paclitaxel 175 mg/m² D1 followed by Gemcitabine 1250 mg/m² D1 and D8 every 3 weeks paclitaxel plus gemcitabine: paclitaxel 175 mg/m² on day 1 plus gemcitabine 1250 mg/m² on days 1
Overall Study STARTED	503	501
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	503	501

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Vinflunine Plus Gemcitabine Versus Paclitaxel Plus Gemcitabine in Patients With Advanced Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vinflunine Plus Gemcitabine n=503 Participants vinflunine 320 mg/m² D1 plus gemcitabine 1000 mg/m2 D1 and D8 every 3 weeks Vinflunine vinflunine plus gemcitabine: 320 mg/m² IV on day 1 plus gemcitabine 1000 mg/m² on days 1 and 8 of each cycle repeated every 3 weeks	Paclitaxel Plus Gemcitabine n=501 Participants paclitaxel 175 mg/m² D1 followed by Gemcitabine 1250 mg/m² D1 and D8 every 3 weeks paclitaxel plus gemcitabine: paclitaxel 175 mg/m² on day 1 plus gemcitabine 1250 mg/m² on days 1	Total n=1004 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	428 Participants n=5 Participants	438 Participants n=7 Participants	866 Participants n=5 Participants
Age, Categorical >=65 years	75 Participants n=5 Participants	63 Participants n=7 Participants	138 Participants n=5 Participants
Age, Continuous	53.2 years n=5 Participants	54.4 years n=7 Participants	53.6 years n=5 Participants
Sex: Female, Male Female	503 Participants n=5 Participants	501 Participants n=7 Participants	1004 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: PFS was calculated from the registration date until the date of progression or death due to any cause if no progression was recorded first (median duration of follow-up: 14.1 months)

Population: ITT population

Outcome measures

Outcome measures
Measure	Vinflunine Plus Gemcitabine n=503 Participants vinflunine 320 mg/m² D1 plus gemcitabine 1000 mg/m2 D1 and D8 every 3 weeks Vinflunine vinflunine plus gemcitabine: 320 mg/m² IV on day 1 plus gemcitabine 1000 mg/m² on days 1 and 8 of each cycle repeated every 3 weeks	Paclitaxel Plus Gemcitabine n=501 Participants paclitaxel 175 mg/m² D1 followed by Gemcitabine 1250 mg/m² D1 and D8 every 3 weeks paclitaxel plus gemcitabine: paclitaxel 175 mg/m² on day 1 plus gemcitabine 1250 mg/m² on days 1
Progression Free Survival	8.0 Months Interval 7.2 to 8.9	8.4 Months Interval 7.6 to 8.9

SECONDARY outcome

Timeframe: OS was evaluated from the date of registration to the date of death due to any cause (median duration of follow-up: 14.1 months)

Population: ITT population - Cut-off date: 30 June 2011

The secondary efficacy parameter was Overall Survival (OS) analysed in the Intent-to-treat (ITT) population. OS was defined as the time elapsed from the date of randomisation up to death or last follow-up.

Outcome measures

Outcome measures
Measure	Vinflunine Plus Gemcitabine n=503 Participants vinflunine 320 mg/m² D1 plus gemcitabine 1000 mg/m2 D1 and D8 every 3 weeks Vinflunine vinflunine plus gemcitabine: 320 mg/m² IV on day 1 plus gemcitabine 1000 mg/m² on days 1 and 8 of each cycle repeated every 3 weeks	Paclitaxel Plus Gemcitabine n=501 Participants paclitaxel 175 mg/m² D1 followed by Gemcitabine 1250 mg/m² D1 and D8 every 3 weeks paclitaxel plus gemcitabine: paclitaxel 175 mg/m² on day 1 plus gemcitabine 1250 mg/m² on days 1
Overall Survival	18.9 Months Interval 16.9 to 22.6	19.1 Months Interval 17.8 to 21.4

SECONDARY outcome

Timeframe: ORR and DCR were calculated from the date of randomisation of first patient until the database cut-off (30 June 2011), assessed up to 5 years

Population: ITT

Disease control rate (DCR) is defined as the sum of Complete Response (CR) and Partial Response (PR) and Stable Disease (SD) ≥ 6 months rate. Objective response rate (ORR) is defined as the sum of Complete Response (CR) and Partial Response (PR) rate (using the best confirmed response recorded from the date of randomisation to the end of treatment). DCR and ORR, assessed by Independent Review Committee using RECIST 1.0, were calculated in the ITT population.

Outcome measures

Outcome measures
Measure	Vinflunine Plus Gemcitabine n=503 Participants vinflunine 320 mg/m² D1 plus gemcitabine 1000 mg/m2 D1 and D8 every 3 weeks Vinflunine vinflunine plus gemcitabine: 320 mg/m² IV on day 1 plus gemcitabine 1000 mg/m² on days 1 and 8 of each cycle repeated every 3 weeks	Paclitaxel Plus Gemcitabine n=501 Participants paclitaxel 175 mg/m² D1 followed by Gemcitabine 1250 mg/m² D1 and D8 every 3 weeks paclitaxel plus gemcitabine: paclitaxel 175 mg/m² on day 1 plus gemcitabine 1250 mg/m² on days 1
Overall Response Rate & Disease Control Rate Overall Response Rate	11.3 percentage of patients Interval 8.7 to 14.4	14.6 percentage of patients Interval 11.6 to 18.0
Overall Response Rate & Disease Control Rate Disease Control Rate	39.8 percentage of patients Interval 35.5 to 44.2	44.9 percentage of patients Interval 40.5 to 49.4

Adverse Events

Vinflunine Plus Gemcitabine

Serious events: 215 serious events

Other events: 494 other events

Deaths: 406 deaths

Paclitaxel Plus Gemcitabine

Serious events: 128 serious events

Other events: 494 other events

Deaths: 394 deaths

Serious adverse events

Other adverse events

Additional Information

Karim Keddad

Institut de Recherche Pierre Fabre

Phone: +33 5 34 50 61 69

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Vinflunine Plus Gemcitabine n=495 participants at risk vinflunine 320 mg/m² D1 plus gemcitabine 1000 mg/m2 D1 and D8 every 3 weeks Vinflunine vinflunine plus gemcitabine: 320 mg/m² IV on day 1 plus gemcitabine 1000 mg/m² on days 1 and 8 of each cycle repeated every 3 weeks	Paclitaxel Plus Gemcitabine n=496 participants at risk paclitaxel 175 mg/m² D1 followed by Gemcitabine 1250 mg/m² D1 and D8 every 3 weeks paclitaxel plus gemcitabine: paclitaxel 175 mg/m² on day 1 plus gemcitabine 1250 mg/m² on days 1
Blood and lymphatic system disorders Anaemia	3.2% 16/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	1.4% 7/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Blood and lymphatic system disorders Febrile neutropenia	3.4% 17/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	1.6% 8/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Blood and lymphatic system disorders Leukopenia	1.4% 7/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.60% 3/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Blood and lymphatic system disorders Neutropenia	10.9% 54/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	2.0% 10/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Blood and lymphatic system disorders Thrombocytopenia	2.4% 12/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.81% 4/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Cardiac disorders Atrial fibrillation	0.61% 3/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.40% 2/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Cardiac disorders Supraventricular tachycardia	0.20% 1/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.00% 0/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Cardiac disorders Ventricular dysfunction	0.20% 1/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.00% 0/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.20% 1/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.00% 0/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Abdominal pain	3.8% 19/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Abdominal pain upper	0.40% 2/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.00% 0/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Anal inflammation	0.20% 1/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.00% 0/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Constipation	5.7% 28/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Diarrhoea	3.8% 19/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	1.2% 6/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Dysphagia	0.40% 2/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.00% 0/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Enterocolitis	0.40% 2/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.00% 0/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Gastritis	0.00% 0/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Ileus	3.4% 17/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Impaired gastric emptying	0.20% 1/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.00% 0/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Intestinal obstruction	0.40% 2/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Nausea	2.2% 11/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Odynophagia	0.20% 1/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.00% 0/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Stomatitis	1.2% 6/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.40% 2/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Vomiting	3.2% 16/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.81% 4/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Asthenia	0.40% 2/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.60% 3/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Chest pain	0.61% 3/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	1.2% 6/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Condition aggravated	1.0% 5/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.60% 3/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Pyrexia	2.2% 11/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	2.6% 13/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Injection site reaction	0.20% 1/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.00% 0/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Hepatobiliary disorders Hepatic function abnormal	0.20% 1/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Hepatobiliary disorders Hyperbilirubinemia	0.20% 1/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Immune system disorders Anaphylactic reaction	0.00% 0/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Immune system disorders Hypersensitivity	0.40% 2/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.60% 3/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Infections and infestations Bronchopneumonia	0.00% 0/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Infections and infestations Catheter-related infection	1.0% 5/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.40% 2/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Infections and infestations Cellulitis	0.40% 2/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Infections and infestations Erysipelas	0.40% 2/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Infections and infestations Gastroenteritis	0.20% 1/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Infections and infestations Infection NOS	0.00% 0/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.40% 2/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Infections and infestations Mastitis	0.00% 0/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	0.20% 1/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)

Other adverse events
Measure	Vinflunine Plus Gemcitabine n=495 participants at risk vinflunine 320 mg/m² D1 plus gemcitabine 1000 mg/m2 D1 and D8 every 3 weeks Vinflunine vinflunine plus gemcitabine: 320 mg/m² IV on day 1 plus gemcitabine 1000 mg/m² on days 1 and 8 of each cycle repeated every 3 weeks	Paclitaxel Plus Gemcitabine n=496 participants at risk paclitaxel 175 mg/m² D1 followed by Gemcitabine 1250 mg/m² D1 and D8 every 3 weeks paclitaxel plus gemcitabine: paclitaxel 175 mg/m² on day 1 plus gemcitabine 1250 mg/m² on days 1
Blood and lymphatic system disorders Anaemia	32.1% 159/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	19.0% 94/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Blood and lymphatic system disorders Leukopenia	6.9% 34/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	5.4% 27/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Blood and lymphatic system disorders Neutropenia	59.6% 295/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	50.2% 249/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Blood and lymphatic system disorders Thrombocytopenia	12.3% 61/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	17.5% 87/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Abdominal pain	35.4% 175/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	17.5% 87/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Abdominal pain upper	14.1% 70/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	7.9% 39/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Constipation	48.3% 239/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	25.4% 126/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Diarrhoea	22.4% 111/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	27.6% 137/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Nausea	53.7% 266/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	44.4% 220/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Stomatitis	34.1% 169/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	17.1% 85/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Vomiting	43.6% 216/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	27.0% 134/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Asthenia	11.3% 56/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	9.3% 46/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Fatigue	63.4% 314/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	57.7% 286/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Injection site reaction	14.9% 74/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	3.8% 19/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Oedema peripheral	15.4% 76/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	17.3% 86/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Pain	9.9% 49/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	8.1% 40/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Pyrexia	25.1% 124/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	26.8% 133/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Investigations Weight decreased	33.5% 166/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	25.4% 126/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Metabolism and nutrition disorders Anorexia	33.1% 164/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	24.0% 119/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Musculoskeletal and connective tissue disorders Arthralgia	14.7% 73/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	18.1% 90/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Musculoskeletal and connective tissue disorders Bone pain	20.4% 101/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	20.8% 103/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Musculoskeletal and connective tissue disorders Myalgia	21.0% 104/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	23.4% 116/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Musculoskeletal and connective tissue disorders Pain in extremity	18.8% 93/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	21.0% 104/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Nervous system disorders Dysgeusia	3.8% 19/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	6.9% 34/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Nervous system disorders Headache	17.8% 88/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	13.3% 66/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Nervous system disorders Paraesthesia	4.4% 22/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	15.1% 75/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Nervous system disorders Peripheral motor neuropathy	2.2% 11/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	6.9% 34/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Nervous system disorders Peripheral sensory neuropathy	13.3% 66/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	45.6% 226/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.5% 126/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	25.8% 128/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Skin and subcutaneous tissue disorders Alopecia	40.8% 202/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	63.9% 317/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Respiratory, thoracic and mediastinal disorders Rash	7.9% 39/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	13.1% 65/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Vascular disorders Phlebitis	7.9% 39/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	2.4% 12/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Blood and lymphatic system disorders Febrile neutropenia	5.1% 25/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	2.6% 13/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Gastrointestinal disorders Dyspepsia	7.3% 36/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	5.4% 27/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Chest pain	11.5% 57/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	9.9% 49/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
General disorders Influenza like illness	7.9% 39/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	7.9% 39/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Infections and infestations Upper respiratory tract infection	5.5% 27/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	6.9% 34/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Infections and infestations Urinary tract infection	7.5% 37/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	7.5% 37/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Investigations Alanine aminotransferase increased	5.1% 25/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	5.4% 27/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)
Investigations Weight increased	8.9% 44/495 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)	13.5% 67/496 • Each subject was assessed for occurrence of Adverse Events throughout the study period (treatment period and follow-up period), up to 8 years. Safety data are presented for the global safety population which include the safety data of the 13 patients ongoing treatment (up to the premature termination date 18 February 2015). Safety population is defined as all treated patients analysed in the treatment arm they received (n=495 subjects in the Vinflunine Plus Gemcitabine arm and n=496 in the Paclitaxel Plus Gemcitabine arm)