Trial Outcomes & Findings for Study of Oral Vinorelbine Plus Capecitabine Versus Taxane-gemcitabine Combinations as 1st Line Chemotherapy in Metastatic Breast Cancer (NCT NCT03887130)

Last Updated: 2024-04-30

Results Overview

Disease control rate (DCR) defined as the sum of complete response, partial response and stable disease for at least 3 months according to RECIST criteria version 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR)= Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. Stable disease: no partial response or progression of the disease

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

152 participants

Primary outcome timeframe

From Baseline to disease progression or death, up to 6 years

Results posted on

2024-04-30

Participant Flow

Participant milestones

Participant milestones
Measure	Vinorelbine-Capecitabine (Arm A) oral vinorelbine (OV) with capecitabine (CAP) oral vinorelbine: Oral vinorelbine 60 mg/m² on day 1 \& day 8, for cycle 1, and then 80 mg/m² on day 1 \& day 8, every 3 weeks for subsequent cycles Capecitabine: Capecitabine 1000 mg/m² twice a day (2000 mg/m² daily) from day 1 to day 14	Gemcitabine-Paclitaxel (Arm B) gemcitabine (GEM) in combination with paclitaxel (PAC) Gemcitabine 1250 mg/m²: Gemcitabine 1250 mg/m² on day 1 \& day 8 Paclitaxel: Paclitaxel 175 mg/m² on day 1	Gemcitabine-Docetaxel (Arm C) gemcitabine (GEM) in combination with docetaxel (DOC) Gemcitabine 1000 mg/m²: Gemcitabine: 1000 mg/m² on day 1 \& 8 Docetaxel: Docetaxel 75 mg/m² on day 1
Overall Study STARTED	51	50	51
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	51	50	51

Reasons for withdrawal

Reasons for withdrawal
Measure	Vinorelbine-Capecitabine (Arm A) oral vinorelbine (OV) with capecitabine (CAP) oral vinorelbine: Oral vinorelbine 60 mg/m² on day 1 \& day 8, for cycle 1, and then 80 mg/m² on day 1 \& day 8, every 3 weeks for subsequent cycles Capecitabine: Capecitabine 1000 mg/m² twice a day (2000 mg/m² daily) from day 1 to day 14	Gemcitabine-Paclitaxel (Arm B) gemcitabine (GEM) in combination with paclitaxel (PAC) Gemcitabine 1250 mg/m²: Gemcitabine 1250 mg/m² on day 1 \& day 8 Paclitaxel: Paclitaxel 175 mg/m² on day 1	Gemcitabine-Docetaxel (Arm C) gemcitabine (GEM) in combination with docetaxel (DOC) Gemcitabine 1000 mg/m²: Gemcitabine: 1000 mg/m² on day 1 \& 8 Docetaxel: Docetaxel 75 mg/m² on day 1
Overall Study Progressive disease	23	14	7
Overall Study Protocol Violation	3	1	2
Overall Study Drug related toxicity	7	7	13
Overall Study Non drug related toxicity	3	0	0
Overall Study Death	2	2	1
Overall Study Withdrawal by Subject	7	6	11
Overall Study other reason	6	20	17

Baseline Characteristics

Study of Oral Vinorelbine Plus Capecitabine Versus Taxane-gemcitabine Combinations as 1st Line Chemotherapy in Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vinorelbine-Capecitabine (Arm A) n=49 Participants oral vinorelbine (OV) with capecitabine (CAP) oral vinorelbine: Oral vinorelbine 60 mg/m² on day 1 \& day 8, for cycle 1, and then 80 mg/m² on day 1 \& day 8, every 3 weeks for subsequent cycles Capecitabine: Capecitabine 1000 mg/m² twice a day (2000 mg/m² daily) from day 1 to day 14	Gemcitabine-Paclitaxel (Arm B) n=50 Participants gemcitabine (GEM) in combination with paclitaxel (PAC) Gemcitabine 1250 mg/m²: Gemcitabine 1250 mg/m² on day 1 \& day 8 Paclitaxel: Paclitaxel 175 mg/m² on day 1	Gemcitabine-Docetaxel (Arm C) n=50 Participants gemcitabine (GEM) in combination with docetaxel (DOC) Gemcitabine 1000 mg/m²: Gemcitabine: 1000 mg/m² on day 1 \& 8 Docetaxel: Docetaxel 75 mg/m² on day 1	Total n=149 Participants Total of all reporting groups
Age, Continuous	56.4 years STANDARD_DEVIATION 9.7 • n=93 Participants	56.0 years STANDARD_DEVIATION 10.8 • n=4 Participants	57.4 years STANDARD_DEVIATION 9.7 • n=27 Participants	56.6 years STANDARD_DEVIATION 10.0 • n=483 Participants
Sex: Female, Male Female	49 Participants n=93 Participants	50 Participants n=4 Participants	50 Participants n=27 Participants	149 Participants n=483 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Body surface area	1.8 mg/m² STANDARD_DEVIATION 0.2 • n=93 Participants	1.7 mg/m² STANDARD_DEVIATION 0.2 • n=4 Participants	1.8 mg/m² STANDARD_DEVIATION 0.2 • n=27 Participants	1.7 mg/m² STANDARD_DEVIATION 0.2 • n=483 Participants
Delay between diagnosis and study entry	5.5 years STANDARD_DEVIATION 5.7 • n=93 Participants	5.8 years STANDARD_DEVIATION 6.3 • n=4 Participants	5.8 years STANDARD_DEVIATION 5.9 • n=27 Participants	5.7 years STANDARD_DEVIATION 5.9 • n=483 Participants
Primary tumour site Bilateral	3 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants
Primary tumour site Left breast	20 Participants n=93 Participants	24 Participants n=4 Participants	29 Participants n=27 Participants	73 Participants n=483 Participants
Primary tumour site Right breast	26 Participants n=93 Participants	26 Participants n=4 Participants	21 Participants n=27 Participants	73 Participants n=483 Participants
Delay between first relapse/progression and study entry	8.8 months STANDARD_DEVIATION 19.1 • n=93 Participants	11.1 months STANDARD_DEVIATION 29.8 • n=4 Participants	11.3 months STANDARD_DEVIATION 23.9 • n=27 Participants	10.4 months STANDARD_DEVIATION 24.5 • n=483 Participants
Categorized number of organs involved at baseline 1 organ	9 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants	16 Participants n=483 Participants
Categorized number of organs involved at baseline 2 organs	14 Participants n=93 Participants	25 Participants n=4 Participants	17 Participants n=27 Participants	56 Participants n=483 Participants
Categorized number of organs involved at baseline >= 3 organs	26 Participants n=93 Participants	22 Participants n=4 Participants	29 Participants n=27 Participants	77 Participants n=483 Participants

PRIMARY outcome

Timeframe: From Baseline to disease progression or death, up to 6 years

Population: Disease control rate was measured in the Intent-to-treat ITT population that consisted of all treated patients.

Outcome measures

Outcome measures
Measure	Vinorelbine-Capecitabine (Arm A) n=49 Participants oral vinorelbine (OV) with capecitabine (CAP) oral vinorelbine: Oral vinorelbine 60 mg/m² on day 1 \& day 8, for cycle 1, and then 80 mg/m² on day 1 \& day 8, every 3 weeks for subsequent cycles Capecitabine: Capecitabine 1000 mg/m² twice a day (2000 mg/m² daily) from day 1 to day 14	Gemcitabine-Paclitaxel (Arm B) n=50 Participants gemcitabine (GEM) in combination with paclitaxel (PAC) Gemcitabine 1250 mg/m²: Gemcitabine 1250 mg/m² on day 1 \& day 8 Paclitaxel: Paclitaxel 175 mg/m² on day 1	Gemcitabine-Docetaxel (Arm C) n=50 Participants gemcitabine (GEM) in combination with docetaxel (DOC) Gemcitabine 1000 mg/m²: Gemcitabine: 1000 mg/m² on day 1 \& 8 Docetaxel: Docetaxel 75 mg/m² on day 1
Disease Control Rate (DCR)	73.5 percentage of participants Interval 58.9 to 85.1	78.0 percentage of participants Interval 64.1 to 88.5	80.0 percentage of participants Interval 66.3 to 90.0

Adverse Events

Vinorelbine-Capecitabine (Arm A)

Serious events: 13 serious events

Other events: 49 other events

Deaths: 31 deaths

Gemcitabine-Paclitaxel (Arm B)

Serious events: 16 serious events

Other events: 50 other events

Deaths: 37 deaths

Gemcitabine-Docetaxel (Arm C)

Serious events: 12 serious events

Other events: 50 other events

Deaths: 35 deaths

Serious adverse events

Other adverse events

Additional Information

Gustavo Villanova M.D

Pierre Fabre

Phone: +33149108265

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Vinorelbine-Capecitabine (Arm A) n=49 participants at risk oral vinorelbine (OV) with capecitabine (CAP) oral vinorelbine: Oral vinorelbine 60 mg/m² on day 1 \& day 8, for cycle 1, and then 80 mg/m² on day 1 \& day 8, every 3 weeks for subsequent cycles Capecitabine: Capecitabine 1000 mg/m² twice a day (2000 mg/m² daily) from day 1 to day 14	Gemcitabine-Paclitaxel (Arm B) n=50 participants at risk gemcitabine (GEM) in combination with paclitaxel (PAC) Gemcitabine 1250 mg/m²: Gemcitabine 1250 mg/m² on day 1 \& day 8 Paclitaxel: Paclitaxel 175 mg/m² on day 1	Gemcitabine-Docetaxel (Arm C) n=50 participants at risk gemcitabine (GEM) in combination with docetaxel (DOC) Gemcitabine 1000 mg/m²: Gemcitabine: 1000 mg/m² on day 1 \& 8 Docetaxel: Docetaxel 75 mg/m² on day 1
Investigations International normalised ratio	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Vascular disorders Haematoma	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Abdominal pain upper	2.0% 1/49 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Constipation	4.1% 2/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Oesophagitis	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Vomiting	10.2% 5/49 • Number of events 5 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Surgical and medical procedures Malignant tumour excision	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Vascular disorders Deep vein thrombosis	2.0% 1/49 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Nausea	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Diarrhoea	8.2% 4/49 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Blood and lymphatic system disorders Neutropenia	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
General disorders Pyrexia	4.1% 2/49 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Injury, poisoning and procedural complications Hip fracture	4.1% 2/49 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Musculoskeletal and connective tissue disorders Back pain	4.1% 2/49 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Injury, poisoning and procedural complications Rib fracture	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Blood and lymphatic system disorders Leukopenia	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
General disorders Condition aggravated	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Metabolism and nutrition disorders Dehydration	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Ileus	4.1% 2/49 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Nervous system disorders Cerebral ischaemia	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Infections and infestations Lower respiratory tract infection	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Nervous system disorders Dysarthria	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Nervous system disorders Dyskinesia	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Nervous system disorders Syncope	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Injury, poisoning and procedural complications Dislocation of joint prosthesis	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Infections and infestations Soft tissue infection	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Infections and infestations Gastroenteritis viral	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
General disorders Fatigue	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Hepatobiliary disorders Hepatic pain	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Infections and infestations Pharyngitis	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Blood and lymphatic system disorders Anaemia	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	4.0% 2/50 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Blood and lymphatic system disorders Thrombocythaemia	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Infections and infestations Pneumonia	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
General disorders Pain	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years

Other adverse events
Measure	Vinorelbine-Capecitabine (Arm A) n=49 participants at risk oral vinorelbine (OV) with capecitabine (CAP) oral vinorelbine: Oral vinorelbine 60 mg/m² on day 1 \& day 8, for cycle 1, and then 80 mg/m² on day 1 \& day 8, every 3 weeks for subsequent cycles Capecitabine: Capecitabine 1000 mg/m² twice a day (2000 mg/m² daily) from day 1 to day 14	Gemcitabine-Paclitaxel (Arm B) n=50 participants at risk gemcitabine (GEM) in combination with paclitaxel (PAC) Gemcitabine 1250 mg/m²: Gemcitabine 1250 mg/m² on day 1 \& day 8 Paclitaxel: Paclitaxel 175 mg/m² on day 1	Gemcitabine-Docetaxel (Arm C) n=50 participants at risk gemcitabine (GEM) in combination with docetaxel (DOC) Gemcitabine 1000 mg/m²: Gemcitabine: 1000 mg/m² on day 1 \& 8 Docetaxel: Docetaxel 75 mg/m² on day 1
Cardiac disorders Sinus tachycardia	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Eye disorders Lacrimation increased	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Abdominal pain	32.7% 16/49 • Number of events 16 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	12.0% 6/50 • Number of events 6 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	18.0% 9/50 • Number of events 9 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Abdominal pain upper	16.3% 8/49 • Number of events 8 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Constipation	14.3% 7/49 • Number of events 7 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	14.0% 7/50 • Number of events 7 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	20.0% 10/50 • Number of events 10 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Diarrhoea	59.2% 29/49 • Number of events 29 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	26.0% 13/50 • Number of events 13 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	38.0% 19/50 • Number of events 19 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Dyspepsia	12.2% 6/49 • Number of events 6 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	12.0% 6/50 • Number of events 6 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Dysphagia	4.1% 2/49 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Haemorrhoids	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Ileus	8.2% 4/49 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	10.0% 5/50 • Number of events 5 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Nausea	59.2% 29/49 • Number of events 29 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	38.0% 19/50 • Number of events 19 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	44.0% 22/50 • Number of events 22 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Stomatitis	22.4% 11/49 • Number of events 11 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	30.0% 15/50 • Number of events 15 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Gastrointestinal disorders Vomiting	55.1% 27/49 • Number of events 27 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	24.0% 12/50 • Number of events 12 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	38.0% 19/50 • Number of events 19 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
General disorders Chest pain	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	12.0% 6/50 • Number of events 6 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
General disorders Chills	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	4.0% 2/50 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
General disorders Fatigue	77.6% 38/49 • Number of events 38 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	70.0% 35/50 • Number of events 35 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	84.0% 42/50 • Number of events 42 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
General disorders Influenza like illness	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
General disorders Oedema peripheral	12.2% 6/49 • Number of events 6 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	26.0% 13/50 • Number of events 13 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
General disorders Pain	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	4.0% 2/50 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
General disorders Pyrexia	12.2% 6/49 • Number of events 6 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	16.0% 8/50 • Number of events 8 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	26.0% 13/50 • Number of events 13 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Immune system disorders Hypersensitivity	0.00% 0/49 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	10.0% 5/50 • Number of events 5 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	12.0% 6/50 • Number of events 6 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Infections and infestations Bronchitis	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Infections and infestations Neutropenic infection	4.1% 2/49 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Infections and infestations Upper respiratory tract infection	8.2% 4/49 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	12.0% 6/50 • Number of events 6 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Infections and infestations Urinary tract infection	8.2% 4/49 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	2.0% 1/50 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Investigations Weight decreased	28.6% 14/49 • Number of events 14 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	14.0% 7/50 • Number of events 7 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	20.0% 10/50 • Number of events 10 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Investigations Weight increased	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Metabolism and nutrition disorders Anorexia	38.8% 19/49 • Number of events 19 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	26.0% 13/50 • Number of events 13 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	34.0% 17/50 • Number of events 17 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Musculoskeletal and connective tissue disorders Arthralgia	4.1% 2/49 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	30.0% 15/50 • Number of events 15 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	18.0% 9/50 • Number of events 9 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Musculoskeletal and connective tissue disorders Back pain	14.3% 7/49 • Number of events 7 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	10.0% 5/50 • Number of events 5 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Musculoskeletal and connective tissue disorders Bone pain	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	4.0% 2/50 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Musculoskeletal and connective tissue disorders Myalgia	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	4.0% 2/50 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Musculoskeletal and connective tissue disorders Pain in extremity	10.2% 5/49 • Number of events 5 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	12.0% 6/50 • Number of events 6 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	4.0% 2/50 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Nervous system disorders Dizziness	12.2% 6/49 • Number of events 6 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	4.0% 2/50 • Number of events 2 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Nervous system disorders Dysgeusia	2.0% 1/49 • Number of events 1 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	10.0% 5/50 • Number of events 5 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	22.0% 11/50 • Number of events 11 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Nervous system disorders Headache	20.4% 10/49 • Number of events 10 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	16.0% 8/50 • Number of events 8 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	16.0% 8/50 • Number of events 8 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Nervous system disorders Paraesthesia	10.2% 5/49 • Number of events 5 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	32.0% 16/50 • Number of events 16 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Nervous system disorders Peripheral motor neuropathy	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	0.00% 0/50 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Nervous system disorders Peripheral sensory neuropathy	24.5% 12/49 • Number of events 12 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	36.0% 18/50 • Number of events 18 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	16.0% 8/50 • Number of events 8 • All adverse events were collected from the first dose of treatment through study completion up to 6 years
Psychiatric disorders Anxiety	6.1% 3/49 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	8.0% 4/50 • Number of events 4 • All adverse events were collected from the first dose of treatment through study completion up to 6 years	6.0% 3/50 • Number of events 3 • All adverse events were collected from the first dose of treatment through study completion up to 6 years