Trial Outcomes & Findings for E7389 Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes (NCT NCT00337103)

NCT ID: NCT00337103

Last Updated: 2020-06-18

Results Overview

OS was measured from the date of randomization until the date of death from any cause, or the last date the participant was known to be alive. Participants who were lost to follow-up or who were alive at the date of data cutoff were censored. The censoring rules for OS were as follows: 1) if the participant was still alive at data cutoff, the date of data cutoff was considered the end date, and 2) if the participant was lost to follow-up before data cutoff, the date they were last known to be alive was considered the end date. Participants who survived past the end of the study were counted as in the full study period. If death occurred after data cutoff, the end date was to be censored at the time of data cutoff.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1276 participants
• Primary outcome timeframe: From date of randomization until date of death from any cause, assessed up to data cutoff date of 12 Mar 2012, or up to approximately 6 years
• Results posted on: 2020-06-18

Participant Flow

A total of 1276 participants were enrolled and screened, of which 174 were screen failures and 1102 were randomized in the study. Of the randomized participants, 1090 participants received the study treatment.

Participant milestones

Measure	Eribulin Mesylate 1.4 mg/m^2 Eribulin mesylate 1.4 milligram per meter square (mg/m\^2) intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day Capecitabine : Capecitabine 2.5 gram per meter square per day (g/m\^2/day) administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Overall Study STARTED	554	548
Overall Study Treated (Safety Population)	544	546
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	554	548

Reasons for withdrawal

Measure	Eribulin Mesylate 1.4 mg/m^2 Eribulin mesylate 1.4 milligram per meter square (mg/m\^2) intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day Capecitabine : Capecitabine 2.5 gram per meter square per day (g/m\^2/day) administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Overall Study Progressive Disease	414	410
Overall Study Adverse Event	45	59
Overall Study Subject Choice	34	27
Overall Study Clinical Progression	27	24
Overall Study Physician Decision	15	14
Overall Study Withdrawal by Subject	8	5
Overall Study Other	5	6
Overall Study Entry Criteria Not Met	4	1
Overall Study Lost to Follow-up	1	2
Overall Study Death	1	0

Baseline Characteristics

E7389 Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes

Baseline characteristics by cohort

Measure	Eribulin Mesylate 1.4 mg/m^2 n=554 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=548 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.	Total n=1102 Participants Total of all reporting groups
Age, Continuous	53.8 years STANDARD_DEVIATION 10.37 • n=5 Participants	52.8 years STANDARD_DEVIATION 10.20 • n=7 Participants	53.3 years STANDARD_DEVIATION 10.29 • n=5 Participants
Sex: Female, Male Female	554 Participants n=5 Participants	548 Participants n=7 Participants	1102 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) White	496 Participants n=5 Participants	495 Participants n=7 Participants	991 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	25 Participants n=5 Participants	19 Participants n=7 Participants	44 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of randomization until date of death from any cause, assessed up to data cutoff date of 12 Mar 2012, or up to approximately 6 years

Population: Data was analyzed using the Intent-to-Treat (ITT) Population defined as all participants who were randomized.

OS was measured from the date of randomization until the date of death from any cause, or the last date the participant was known to be alive. Participants who were lost to follow-up or who were alive at the date of data cutoff were censored. The censoring rules for OS were as follows: 1) if the participant was still alive at data cutoff, the date of data cutoff was considered the end date, and 2) if the participant was lost to follow-up before data cutoff, the date they were last known to be alive was considered the end date. Participants who survived past the end of the study were counted as in the full study period. If death occurred after data cutoff, the end date was to be censored at the time of data cutoff.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=554 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=548 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Overall Survival (OS)	484 days Interval 462.0 to 536.0	440 days Interval 400.0 to 487.0

PRIMARY outcome

Timeframe: From date of randomization to the date of disease progression or death (whichever occurred first), assessed up to data cutoff date of 12 Mar 2012 or up to approximately 6 years

Population: Data was analyzed using the ITT Population defined as all participants who were randomized.

PFS was defined as the time (in days) from the date of randomization to the date of the first sign of disease progression based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (v 1.1) or date of death, regardless of cause. Disease progression was measured by computed tomography (CT) and magnetic resonance imaging (MRI) performed on lesions targeted at baseline for tumor assessment. Disease progression (as assessed by independent review of the imaging scans) per RECIST v 1.1 was defined as at least a 20% increase in the sum of the diameters of the target lesions (taking as reference the smallest sum on study, including the baseline sum if that is the smallest), and an absolute increase of at least 5 millimeter (mm). Note that the appearance of one or more new lesions was also considered as disease progression.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=554 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=548 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Progression Free Survival (PFS)	126 Days Interval 106.0 to 131.0	129 Days Interval 120.0 to 147.0

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Data was analyzed using the ITT Population defined as all participants who were randomized. Here,"overall number of participants analyzed" are the participants who were evaluable for this outcome measure.

EORTC-QLQ-C30:cancer-specific instrument with 30 questions to assess the participant QoL. First 28 questions used to evaluate 5 functional scales (physical, role, cognitive, emotional, social), 3 symptom scales (fatigue, nausea and vomiting, pain) and other single items(dyspnoea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Each of these 28 questions assessed on 4-point scale(1=not at all, 2=a little, 3=quite a bit, 4=very much); functional scales: higher score=better level of functioning; symptom scale: higher score=more severe symptoms; for single items: higher score= more severe problem. Last 2 questions used to evaluate global health status (GHS)/QoL. Each question was assessed on 7-point scale (1=very poor to 7=excellent). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=438 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=406 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Change From Baseline in Global Health Status/Quality of Life (QoL) Measured by European Organization for the Treatment of Cancer Quality of Life Core Questionnaire Scores Based on Core 30 Items (EORTC-QLQ-C30) at Week 6	0.1 units on a scale Standard Deviation 19.23	1.7 units on a scale Standard Deviation 20.69

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Data was analyzed using the ITT Population defined as all participants who were randomized. Here,"number analyzed" signifies the participants who were evaluable for this outcome measure for individual row.

EORTC-QLQ-BR23:disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess quality of life of participants with breast cancer. The scores from 23 items of QLQ-BR23 included functional scales (body image, sexual functioning, sexual enjoyment, future perspective), symptom scales (systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss). Each item was rated on a scale of 1 to 4 to record level of intensity (1= not at all, 2= a little, 3= quite a bit, 4= very much) within each scales. Scores averaged and transformed to 0-100 scale. High score indicated high/better level of functioning/healthy functioning. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=554 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=548 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Change From Baseline in European Organization for the Treatment of Cancer Quality of Life Core Questionnaire Scores Based on Breast Cancer Specific 23 Items (EORTC-QLQ- BR 23) at Week 6 Body Image	0.7 units on a scale Standard Deviation 21.26	4.8 units on a scale Standard Deviation 21.80
Change From Baseline in European Organization for the Treatment of Cancer Quality of Life Core Questionnaire Scores Based on Breast Cancer Specific 23 Items (EORTC-QLQ- BR 23) at Week 6 Sexual functioning	1.2 units on a scale Standard Deviation 14.75	-0.1 units on a scale Standard Deviation 16.62
Change From Baseline in European Organization for the Treatment of Cancer Quality of Life Core Questionnaire Scores Based on Breast Cancer Specific 23 Items (EORTC-QLQ- BR 23) at Week 6 Sexual enjoyment	0.8 units on a scale Standard Deviation 21.58	3.1 units on a scale Standard Deviation 17.49
Change From Baseline in European Organization for the Treatment of Cancer Quality of Life Core Questionnaire Scores Based on Breast Cancer Specific 23 Items (EORTC-QLQ- BR 23) at Week 6 Future perspective	7.7 units on a scale Standard Deviation 28.48	10.0 units on a scale Standard Deviation 30.84
Change From Baseline in European Organization for the Treatment of Cancer Quality of Life Core Questionnaire Scores Based on Breast Cancer Specific 23 Items (EORTC-QLQ- BR 23) at Week 6 Systemic therapy side effects	4.5 units on a scale Standard Deviation 15.55	-1.2 units on a scale Standard Deviation 14.73
Change From Baseline in European Organization for the Treatment of Cancer Quality of Life Core Questionnaire Scores Based on Breast Cancer Specific 23 Items (EORTC-QLQ- BR 23) at Week 6 Breast Symptoms	-3.4 units on a scale Standard Deviation 16.55	-3.6 units on a scale Standard Deviation 16.20
Change From Baseline in European Organization for the Treatment of Cancer Quality of Life Core Questionnaire Scores Based on Breast Cancer Specific 23 Items (EORTC-QLQ- BR 23) at Week 6 Arm Symptoms	-4.2 units on a scale Standard Deviation 17.94	-3.4 units on a scale Standard Deviation 18.65
Change From Baseline in European Organization for the Treatment of Cancer Quality of Life Core Questionnaire Scores Based on Breast Cancer Specific 23 Items (EORTC-QLQ- BR 23) at Week 6 Upset by hair loss	-4.4 units on a scale Standard Deviation 32.66	-10.1 units on a scale Standard Deviation 29.76

SECONDARY outcome

Timeframe: From date of randomization until date of first documentation of CR or PR, assessed up to data cutoff date of 12 Mar 2012 or up to approximately 6 years

Population: Data was analyzed using the ITT Population defined as all participants who were randomized.

ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v 1.1). CR is defined as disappearance of all target legions and non-target lesions. All pathological lymph nodes (whether target and non-target), must have reduction in their short axis to less than 10 mm. PR is defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=554 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=548 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Objective Response Rate (ORR): Independent Review	11.0 percentage of participants Interval 8.5 to 13.9	11.5 percentage of participants Interval 8.9 to 14.5

SECONDARY outcome

Timeframe: From first documented CR or PR until date of recurrent or progressive disease or death, assessed up to data cutoff of date of 12 Mar 2012 or up to approximately 6 years

Population: Data was analyzed using for a subset of participants in the ITT Population who had a response. Here, "overall number of participants analyzed" are the participants who were evaluable for this outcome measure.

DOR was defined as the time from first documented CR or PR until disease progression or death from any cause for those participants with a confirmed PR or CR measured by RECIST v1.1. CR defined as disappearance of all target and non-target lesions. All pathological lymph nodes(whether target and non-target), must have reduction in their short axis to less than 10 mm. PR defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=61 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=63 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Duration of Response (DOR): Independent Review	198 days Interval 150.0 to 273.0	330 days Interval 208.0 to 541.0

SECONDARY outcome

Timeframe: From the date of randomization to Year 1, 2 and 3

Population: Data was analyzed using the ITT Population defined as all participants who were randomized.

One-, two-, and three- year's survival rates were defined as the percentage of participants who were alive at one, two, and three years respectively, and estimated using the Kaplan-Meier method and Greenwood Formula.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=554 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=548 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Overall Survival Rate At 1-year	0.644 percentage of participants Interval 0.604 to 0.684	0.580 percentage of participants Interval 0.538 to 0.622
Overall Survival Rate At 2-years	0.328 percentage of participants Interval 0.289 to 0.368	0.298 percentage of participants Interval 0.259 to 0.337
Overall Survival Rate At 3-years	0.178 percentage of participants Interval 0.144 to 0.212	0.145 percentage of participants Interval 0.113 to 0.177

SECONDARY outcome

Timeframe: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)

Population: Data was analyzed using the ITT Population defined as all participants who were randomized. Here, "overall number of participants analyzed" are the participants who were evaluable for the outcome measure.

Pain intensity was measured by marking a single vertical line that crosses a 1-100 mm unmarked VAS scale. The left-end of the visual analog scale was labelled "least possible pain" and the right-end of the visual analog scale was labelled "worst possible pain". The pain rating ranged from 0 to 100, with a higher score indicating more pain. A negative change score indicated improvement.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=431 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=431 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Change From Baseline in Pain Intensity by Visual Analog Scale (VAS) Until 30 Days After the Last Dose of Study Drug	-3.7 units on a scale Standard Deviation 22.80	0.4 units on a scale Standard Deviation 22.90

SECONDARY outcome

Timeframe: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)

Population: Data was analyzed using safety population defined as all participants who received at least one dose of study treatment.

Participants took analgesics as concomitant pain medications which are defined as pain medications that (1) started before the first dose of study drug and were continuing at the time of the first dose of study drug, or (2) started on/after the day of the first dose of study drug up to 30 days after the last dose of study drug medication

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=544 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=546 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Number of Participants With Consumption of Analgesics During the Study	222 Participants	196 Participants

SECONDARY outcome

Timeframe: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)

Population: Data was analyzed using safety population defined as all participants who received at least one dose of study treatment.

TEAEs included both SAEs as well as non-SAEs.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=544 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=546 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	512 Participants	494 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	95 Participants	115 Participants

SECONDARY outcome

Timeframe: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)

Population: Data was analyzed using safety population defined as all participants who received at least one dose of study treatment.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=544 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=546 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Parameter Values	362 Participants	224 Participants

SECONDARY outcome

Timeframe: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)

Population: Data was analyzed using safety population defined as all participants who received at least one dose of study treatment.

Concomitant medications included medications that either (1) started before the first dose of study drug and were continuing at the time of the first dose of study drug, or (2) started on or after the first dose of study drug up to 30 days after the last dose of study drug.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=544 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=546 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Number of Participants Who Took at Least One Concomitant Medication	496 Participants	483 Participants

SECONDARY outcome

Timeframe: Up to approximately 6 years for primary analysis completion stage, Up to approximately 6 years 2 months for final analysis completion stage

Population: Data was analyzed using safety population defined as all participants who received at least one dose of study treatment. Here, "number analyzed" signifies the participants who were evaluable at individual stage for this outcome measure.

Data have been reported per primary analysis completion stage and final analysis completion stage. After primary analysis completion (at cutoff date of 12 March 2012), only 10 participants were still receiving study treatment.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=544 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day n=546 Participants Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Duration of Eribulin Mesylate Exposure At primary analysis completion stage	125.0 days Interval 21.0 to 1372.0	119.0 days Interval 21.0 to 1442.0
Duration of Eribulin Mesylate Exposure At final analysis completion stage	1743.0 days Interval 1561.0 to 2219.0	1506.0 days Interval 1175.0 to 2296.0

SECONDARY outcome

Timeframe: Cycle 1 Day 1: 5-10 minutes(min), 15-30 min, 30-60 min, 60-90 min, 2-4 hours(hrs), 4-8 hrs, 10-24 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs after the start of infusion of Eribulin mesylate (Duration of each cycle is 21 days)

Population: Pharmacokinetic (PK) analysis set included all participants who have received at least one dose of E7389 and have at least one quantifiable E7389 concentration. Here, "number analyzed" signifies the participants who were evaluable for this outcome measure for given time points.

Outcome measures

Measure	Eribulin Mesylate 1.4 mg/m^2 n=173 Participants Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.	Capecitabine 2.5 g/m^2/Day Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days.
Plasma Concentrations of Eribulin Mesylate 5-10 minutes	415.8 nanogram per milliliter (ng/mL) Standard Deviation 719.5	—
Plasma Concentrations of Eribulin Mesylate 15-30 minutes	152.6 nanogram per milliliter (ng/mL) Standard Deviation 70.51	—
Plasma Concentrations of Eribulin Mesylate 30-60 minutes	95.5 nanogram per milliliter (ng/mL) Standard Deviation 87.90	—
Plasma Concentrations of Eribulin Mesylate 60-90 minutes	52.7 nanogram per milliliter (ng/mL) Standard Deviation 79.33	—
Plasma Concentrations of Eribulin Mesylate 2-4 hours	20.7 nanogram per milliliter (ng/mL) Standard Deviation 32.81	—
Plasma Concentrations of Eribulin Mesylate 4-8 hours	10.0 nanogram per milliliter (ng/mL) Standard Deviation 5.40	—
Plasma Concentrations of Eribulin Mesylate 10-24 hours	5.8 nanogram per milliliter (ng/mL) Standard Deviation 3.72	—
Plasma Concentrations of Eribulin Mesylate 48-72 hours	3.7 nanogram per milliliter (ng/mL) Standard Deviation 2.58	—
Plasma Concentrations of Eribulin Mesylate 72-96 hours	2.4 nanogram per milliliter (ng/mL) Standard Deviation 1.60	—
Plasma Concentrations of Eribulin Mesylate 96-120 hours	7.6 nanogram per milliliter (ng/mL) Standard Deviation 38.75	—

Adverse Events

Eribulin Mesylate 1.4 mg/m^2

Serious events: 95 serious events

Other events: 509 other events

Deaths: 442 deaths

Capecitabine 2.5 g/m^2/Day

Serious events: 115 serious events

Other events: 489 other events

Deaths: 459 deaths

Serious adverse events

Measure	Eribulin Mesylate 1.4 mg/m^2 n=544 participants at risk Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days	Capecitabine 2.5 g/m^2/Day n=546 participants at risk Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days
General disorders Multi-Organ Failure	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Extravasation	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Influenza Like Illness	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Sudden Death	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Mucosal Inflammation	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Generalized Edema	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Injection Site Extravasation	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Oedema Peripheral	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Headache	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.73% 4/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Cerebrovascular Accident	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Spinal Cord Compression	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Convulsion	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Dizziness	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Facial Paresis	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Myoclonic Epilepsy	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Partial Seizures	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Peripheral Motor Neuropathy	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Peripheral Sensory Neuropathy	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Syncope	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Transient Ischaemic Attack	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Depressed Level of Consciousness	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Aphasia	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Cerebellar Infarction	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Coma Hepatic	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Dysgeuesia	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Intracranial Pressure Increased	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Lethargy	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Simple Partial Seizures	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Somnolence	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Pneumonia	0.74% 4/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.73% 4/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Sepsis	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.73% 4/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Bronchopneumonia	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Hepatitis C	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Lung Infection	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Pneumonia Klebsiella	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Respiratory Tract Infection	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Soft Tissue Infection	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Upper Respiratory Tract Infection	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Urinary Tract Infection	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Bronchitis	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.55% 3/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Cellulitis	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Staphylococcal Infection	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Subcutaneous Abscess	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm Malignant	1.3% 7/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.73% 4/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Liver	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Meninges	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Ovary	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Peritoneum	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oncologic Complication	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour Pain	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Ascites	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Pleural Effusion	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Central Nervous System	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Pleura	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal Cancer	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Vomiting	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	1.6% 9/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal Pain	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	2.7% 15/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Nausea	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	1.3% 7/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Haematemesis	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Haematochezia	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Haemorrhoids	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Intestinal Ischaemia	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Dysphagia	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Constipation	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Cardiopulmonary Failure	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Myocardial Infarction	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Pericardial Effusion	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Angina Pectoris	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Left Ventricular Dysfunction	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Tachycardia	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Cardiac Failure	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Bradycardia	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Cardiac Tamponade	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Cardio-respiratory Arrest	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Cardiac disorders Cardiogenic Shock	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Femur Fracture	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Accidental Overdose	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Femoral Neck Fracture	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Hip Fracture	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Humerus Fracture	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Lumbar Vertebral Fracture	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Joint Dislocation	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Dehydration	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	1.6% 9/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Decreased Appetite	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypercalcaemia	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Electrolyte Imbalance	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Vascular disorders Deep Vein Thrombosis	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.55% 3/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Vascular disorders Hypotension	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Vascular disorders Thrombophlebitis	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Vascular disorders Hypertension	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Vascular disorders Shock Haemorrhagic	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Vascular disorders Thrombosis	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back Pain	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Pathological Fracture	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Bone Pain	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Hepatobiliary disorders Hepatitis Toxic	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Hepatobiliary disorders Hepatic Failure	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Hepatobiliary disorders Cholelithiasis	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Renal and urinary disorders Renal Failure	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Renal and urinary disorders Renal Failure Acute	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Renal and urinary disorders Haematuria	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Renal and urinary disorders Hydronephrosis	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Investigations Haemoglobin Decreased	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Investigations Aspartate Aminotransferase Increased	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Investigations Hepatic Enzyme Increased	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Investigations Troponin Increased	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Immune system disorders Hypersensitivity	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Ear and labyrinth disorders Vertigo	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Palmar-Plantar Erythrodysaesthesia	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Vaginal Haemorrhage	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Surgical and medical procedures Malignant Breast Lump Removal	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Intestinal Obstruction	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Stomatitis	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Vascular disorders Haemorrhage	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Psychiatric disorders Confusional State	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Psychiatric disorders Mental status changes	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.4% 13/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	3.1% 17/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.92% 5/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	1.3% 7/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.55% 3/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Tracheal Stenosis	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea Exertional	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Neutropenia	1.8% 10/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Febrile Neutropenia	1.3% 7/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.73% 4/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Leukopenia	0.74% 4/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Anaemia	0.55% 3/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.00% 0/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Pancytopenia	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.18% 1/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Pyrexia	0.55% 3/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.92% 5/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Asthenia	0.55% 3/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.73% 4/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Fatigue	0.55% 3/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.73% 4/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Death	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.37% 2/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders General Physical Health Deterioration	0.37% 2/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	0.55% 3/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.

Other adverse events

Measure	Eribulin Mesylate 1.4 mg/m^2 n=544 participants at risk Eribulin mesylate 1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days	Capecitabine 2.5 g/m^2/Day n=546 participants at risk Capecitabine : Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days
Blood and lymphatic system disorders Neutropenia	53.7% 292/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	15.9% 87/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Leukopenia	31.4% 171/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	10.4% 57/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Anaemia	18.8% 102/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	17.6% 96/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Thrombocytopenia	5.0% 27/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	5.3% 29/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Fatigue	16.7% 91/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	15.0% 82/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Asthenia	15.3% 83/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	14.5% 79/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Pyrexia	12.3% 67/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	4.9% 27/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Oedema Peripheral	6.4% 35/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	6.6% 36/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
General disorders Mucosal Inflammation	4.8% 26/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	6.4% 35/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Nausea	22.2% 121/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	24.0% 131/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	14.2% 77/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	28.2% 154/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Vomiting	11.6% 63/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	16.3% 89/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Constipation	7.7% 42/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	8.4% 46/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal Pain	5.9% 32/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	8.4% 46/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal Pain Upper	5.7% 31/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	7.1% 39/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Gastrointestinal disorders Stomatitis	5.0% 27/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	5.7% 31/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Alopecia	34.6% 188/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	4.0% 22/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Peripheral Sensory Neuropathy	13.4% 73/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	7.0% 38/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Headache	12.3% 67/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	10.1% 55/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Nervous system disorders Dizziness	5.5% 30/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	5.3% 29/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back Pain	10.1% 55/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	7.9% 43/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Bone Pain	9.2% 50/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	7.7% 42/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in Extremity	8.6% 47/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	6.8% 37/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 42/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	5.7% 31/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Myalgia	5.5% 30/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	1.5% 8/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Infections and infestations Urinary Tract Infection	5.3% 29/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	4.8% 26/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.0% 49/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	9.3% 51/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 45/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	8.1% 44/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Decreased Appetite	12.5% 68/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	14.7% 80/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Investigations Alanine Aminotransferase Increased	8.6% 47/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	4.2% 23/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Investigations Aspartate Aminotransferase Increased	7.9% 43/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	4.9% 27/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour Pain	5.3% 29/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	4.0% 22/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Hepatobiliary disorders Hyperbilirubinaemia	1.7% 9/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	7.0% 38/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Palmar-Plantar Erythrodysaesthesia Syndrome	0.18% 1/544 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.	44.7% 244/546 • First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months) Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment.

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: 1-888-274-2378

Email: esi_oncmedinfo@eisai.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place