Trial Outcomes & Findings for A Study Comparing Eribulin Mesylate and Ixabepilone in Causing or Exacerbating Neuropathy in Participants With Advanced Breast Cancer (NCT NCT00879086)

Last Updated: 2023-06-22

Results Overview

Neuropathy AEs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and coded according to the current version of the Medical Dictionary for Regulatory Activities (MedDRA). Neuropathy AEs included the broad list of preferred terms (PTs) defined in the Standard MedDRA Query for Neuropathy and the following additional PTs: neuropathy, hyperesthesia, painful response to normal stimuli, pallanesthesia, and allodynia. If the post-baseline maximum CTCAE grade of the combined term "neuropathy" was greater than the baseline maximum CTCAE grade of the combined term, then the event was considered as treatment emergent neuropathy adverse events per CTCAE grade. For a single participant, 1) a neuropathy AE occurring more than once during the study, whether defined with the same or different MedDRA PTs, was counted only once, 2) a neuropathy AE with different CTCAE grades had only the highest grade AE counted.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

104 participants

Primary outcome timeframe

From administration of first dose up to approximately 5 years

Results posted on

2023-06-22

Participant Flow

127 participants were screened. Of these, 104 participants were enrolled and randomized into the study and 23 participants were screen failures (19 failed to meet entrance criteria, 3 failed due to other reason, and 1 failed due to consent withdrawal).

Participant milestones

Participant milestones
Measure	Eribulin Mesylate Eribulin mesylate was given at a dose of 1.4 milligram per square meter (mg/m\^2) as a 2 to 5 minute intravenous (IV) bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Overall Study STARTED	52	52
Overall Study Safety Analysis Set (SAS)	51	50
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	52	52

Reasons for withdrawal

Reasons for withdrawal
Measure	Eribulin Mesylate Eribulin mesylate was given at a dose of 1.4 milligram per square meter (mg/m\^2) as a 2 to 5 minute intravenous (IV) bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Overall Study Adverse Event	3	15
Overall Study Participant choice	2	2
Overall Study Progression of disease	40	26
Overall Study Withdrawal of consent	2	1
Overall Study Other	4	6
Overall Study Death	1	2

Baseline Characteristics

A Study Comparing Eribulin Mesylate and Ixabepilone in Causing or Exacerbating Neuropathy in Participants With Advanced Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eribulin Mesylate n=51 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=50 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Total n=101 Participants Total of all reporting groups
Age, Continuous	52.2 Years STANDARD_DEVIATION 9.83 • n=5 Participants	56.9 Years STANDARD_DEVIATION 10.68 • n=7 Participants	54.5 Years STANDARD_DEVIATION 10.49 • n=5 Participants
Sex/Gender, Customized Female	51 Participants n=5 Participants	50 Participants n=7 Participants	101 Participants n=5 Participants
Sex/Gender, Customized Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From administration of first dose up to approximately 5 years

Population: SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=51 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=50 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Percentage of Participants With Treatment-Emergent Neuropathy Adverse Events (AEs)	33.3 Percentage of participants Interval 20.8 to 47.9	50.0 Percentage of participants Interval 35.5 to 64.5

SECONDARY outcome

Timeframe: From administration of first dose up to approximately 5 years

Population: SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication.

The incidence rate of TE myalgia/arthralgia was calculated as the percent of participants with TE myalgia/arthralgia. A participant who had an arthralgia or myalgia AE more than once over the course of the study was counted only once in the incidence calculation for myalgia/arthralgia AEs. A participant who had myalgia/arthralgia AEs with different CTCAE grades was counted with the highest CTCAE grade over the course of the evaluation period. If the post-baseline CTCAE grade of the combined term "Myalgia/Arthralgia" was greater than the baseline maximum CTCAE grade of the combined term, the participant had TE myalgia/arthralgia. The 2-sided 95% confidence interval (CI) for incidence rate of TE myalgia/arthralgia was calculated using the Clopper-Pearson method (i.e., the exact method) for each treatment group.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=51 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=50 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Percentage of Participants With an Incidence of Treatment-emergent Myalgia/Arthralgia	19.6 Percentage of participants Interval 9.8 to 33.1	38.0 Percentage of participants Interval 24.7 to 52.8

SECONDARY outcome

Timeframe: Baseline, Treatment Phase: Cycles 2 to 6 (Day 1); Extension Phase: Cycle 9 Day 1, Cycle 12 Day 1, Cycle 15 Day 1 (Each Cycle length=21 days), End of Treatment, Post-treatment Follow-up, Worst Post-baseline result (Up to approximately 5 years)

Population: SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication. Here "number analyzed" signifies participants who were evaluable for this outcome measure at given time points.

The participant-reported questionnaire was used to compare the incidence and severity of neuropathy AEs. Sensory and motor scores were to be analyzed separately using a generalized linear model. Separate subgroup analyses were performed by each stratification variable. VPAT was measured using a Vibratron II device (Physitemp, Inc.) and a modified Two Alternative Forced Choice psychophysical algorithm. VPT was assessed on the ventral surface of the distal index finger (side opposite the nail), contralateral to the side of the mastectomy or primary disease and on the distal fleshy pad of both the right and left great toes (side opposite the nail). If the mastectomy was bilateral, the index finger on the side without axillary lymph node dissection was tested. Data ranged from 0 (invalid) to 20 vu. A lower VPT indicated a greater sensitivity.

Outcome measures

SECONDARY outcome

Timeframe: Baseline up to approximately 5 years

Population: SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. The participant was told that there was no right or wrong answer and their answer should reflect how they currently felt since last completing the PNQ. Sensory scores were analyzed separately. Letter scores (A= none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A (none)=0, B (mild)=1, C (moderate)=2, D (moderate to severe)=3 and E (severe)=4). Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. Neuropathy AEs that were sensory were evaluated with the PNQ Item 1 (sensory). Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=48 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=46 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) A (Baseline) to A (Worst Post-baseline)	8 Participants	7 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) A (Baseline) to B (Worst Post-baseline)	9 Participants	3 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) A (Baseline) to C (Worst Post-baseline)	5 Participants	4 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) A (Baseline) to D (Worst Post-baseline)	2 Participants	4 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) A (Baseline) to E (Worst Post-baseline)	0 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) B (Baseline) to A (Worst Post-baseline)	1 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) B (Baseline) to B (Worst Post-baseline)	5 Participants	4 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) B (Baseline) to C (Worst Post-baseline)	2 Participants	8 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) B (Baseline) to D (Worst Post-baseline)	9 Participants	5 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) B (Baseline) to E (Worst Post-baseline)	1 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) C (Baseline) to B (Worst Post-baseline)	0 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) C (Baseline) to C (Worst Post-baseline)	3 Participants	4 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) C (Baseline) to D (Worst Post-baseline)	2 Participants	3 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) D (Baseline) to D (Worst Post-baseline)	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to approximately 5 years

Population: SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. The participant was told that there was no right or wrong answer and their answer should reflect how they currently felt since last completing the PNQ. Motor scores were analyzed separately. Letter scores (A= none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A (none)=0, B (mild)=1, C (moderate)=2, D (moderate to severe)=3 and E (severe)=4). Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. Neuropathy AEs that were motor were evaluated with the PNQ Item 2 (motor). Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=48 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=46 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) A (Baseline) to A (Worst Post-baseline)	8 Participants	12 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) A (Baseline) to B (Worst Post-baseline)	12 Participants	3 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) A (Baseline) to C (Worst Post-baseline)	8 Participants	6 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) A (Baseline) to D (Worst Post-baseline)	2 Participants	7 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) A (Baseline) to E (Worst Post-baseline)	0 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) B (Baseline) to B (Worst Post-baseline)	5 Participants	5 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) B (Baseline) to C (Worst Post-baseline)	4 Participants	2 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) B (Baseline) to D (Worst Post-baseline)	4 Participants	4 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) C (Baseline) to C (Worst Post-baseline)	0 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) C (Baseline) to D (Worst Post-baseline)	0 Participants	4 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) D (Baseline) to A (Worst Post-baseline)	1 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) D (Baseline) to D (Worst Post-baseline)	3 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) D (Baseline) to E (Worst Post-baseline)	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to approximately 5 years

Population: SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. Sensory scores, motor scores and composite scores were analyzed separately. For both item 1 and item 2, letter scores (A=none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A(none)=0, B(mild)=1, C(moderate)=2, D(moderate to severe)=3 and E (severe)=4. Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. PNQ composite score was defined as the worst of Item 1 and Item 2 score. If neither Item 1 or item 2 score was D or E, but if a box was checked in Item 3, PNQ composite score would be D. Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=48 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=46 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score A (Baseline) to A (Worst Post-baseline)	3 Participants	5 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score A (Baseline) to B (Worst Post-baseline)	6 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score A (Baseline) to C (Worst Post-baseline)	5 Participants	2 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score A (Baseline) to D (Worst Post-baseline)	2 Participants	5 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score A (Baseline) to E (Worst Post-baseline)	0 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score B (Baseline) to A (Worst Post-baseline)	0 Participants	1 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score B (Baseline) to B (Worst Post-baseline)	5 Participants	6 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score B (Baseline) to C (Worst Post-baseline)	5 Participants	6 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score B (Baseline) to D (Worst Post-baseline)	9 Participants	6 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score C (Baseline) to C (Worst Post-baseline)	2 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score C (Baseline) to D (Worst Post-baseline)	1 Participants	3 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score D (Baseline) to A (Worst Post-baseline)	1 Participants	0 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score D (Baseline) to C (Worst Post-baseline)	0 Participants	2 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score D (Baseline) to D (Worst Post-baseline)	7 Participants	7 Participants
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score D (Baseline) to E (Worst Post-baseline)	2 Participants	1 Participants

SECONDARY outcome

Timeframe: From date of treatment start until disease progression (PD) (Up to approximately 5 years)

Population: Full analysis set (FAS) included all randomized participants.

ORR was defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 for target lesions assessed by magnetic resonance imaging and computed tomography and investigator assessment. Participants with unknown or missing responses were treated as non-responders. CR was defined as disappearance of all target lesions. PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. ORR=CR+PR, was presented with 2-sided 95% confidence interval (CI) by the method of Clopper-Pearson method for calculating the exact binomial intervals.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=52 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=52 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Objective Response Rate (ORR)	15.4 Percentage of participants Interval 6.9 to 28.1	5.8 Percentage of participants Interval 1.2 to 15.9

SECONDARY outcome

Timeframe: From date of treatment start until the date of PD or death from any cause (Up to approximately 5 years)

Population: FAS analysis set included all randomized participants.

PFS was defined as the time from randomization until PD or death due to any cause as determined by the investigator. Disease progression per RECIST v1.0 was defined as at least a 20% relative increase and 5 millimeter absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. The duration of PFS was calculated as the end date minus date of first drug plus 1. For participants who did not have an event (those lost to follow-up or who had not progressed at the date of data cut-off) PFS was censored. The median PFS and corresponding 95% CI was estimated for each treatment group using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=52 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=52 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Progression-Free Survival (PFS)	104 Days Interval 80.0 to 129.0	95 Days Interval 73.0 to 186.0

SECONDARY outcome

Timeframe: From date of treatment start until PD or death from any cause, whichever occurred first (Up to approximately 5 years)

Population: FAS analysis set included all randomized participants.

CBR was defined as the number of participants (CR + PR + stable disease (SD) greater than or equal to 6 months) divided by the number of participants in the analysis population. The 95% CI was generated for the clinical benefit rate for each treatment group, and it was based on the Clopper-Pearson method for calculating the exact binomial intervals.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=52 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=52 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Clinical Benefit Rate (CBR)	26.9 Percentage of participants Interval 15.6 to 41.0	21.2 Percentage of participants Interval 11.1 to 34.7

SECONDARY outcome

Timeframe: From date of first CR or PR until the first documentation of PD or date of death (Up to approximately 5 years)

Population: FAS analysis set included all randomized participants. Number of participants analyzed who had CR or PR.

DoR was defined as the time from first documented CR or PR until PD or death from any cause. It was measured from the time that measurement criteria were met for CR or PR (whichever status was recorded first) until the first date that recurrent or PD was objectively documented. It was defined for participants with a confirmed CR or a confirmed PR. Participants without progressive disease or death were censored. Median duration and 95% CI of the median were estimated for each treatment group, using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=8 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=3 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Duration of Response (DoR)	169 Days Interval 60.0 to 246.0	NA Days Here, Median and 95% upper and lower CI could not be estimated due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: For each participant, from the first dose till 42 days after the last dose of study treatment (Up to approximately 5 years)

Population: SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication.

General safety was assessed by monitoring all TEAEs and SAEs. TEAEs were reported at a frequency of 0% or greater in the study population.

Outcome measures

Outcome measures
Measure	Eribulin Mesylate n=51 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=50 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Eribulin and Ixabepilone TEAEs	100.0 Percentage of participants	100.0 Percentage of participants
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Eribulin and Ixabepilone SAEs	37.3 Percentage of participants	34.0 Percentage of participants

Adverse Events

Eribulin Mesylate

Serious events: 19 serious events

Other events: 51 other events

Deaths: 2 deaths

Ixabepilone

Serious events: 17 serious events

Other events: 50 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: 888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Eribulin Mesylate n=51 Participants Eribulin mesylate was given at a dose of 1.4 mg/m\^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).	Ixabepilone n=50 Participants Ixabepilone was given at a starting dose of 32 or 40 mg/m\^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
Change From Baseline in Vibration Perception Threshold (VPT) Index Finger, Baseline	1.50 Vibration units (vu) Standard Deviation 1.117	1.96 Vibration units (vu) Standard Deviation 1.373
Change From Baseline in Vibration Perception Threshold (VPT) Index Finger, Cycle 2 (Day 1)	0.13 Vibration units (vu) Standard Deviation 1.196	-0.09 Vibration units (vu) Standard Deviation 1.641
Change From Baseline in Vibration Perception Threshold (VPT) Index Finger, Cycle 3 (Day 1)	0.31 Vibration units (vu) Standard Deviation 0.478	-0.22 Vibration units (vu) Standard Deviation 1.762
Change From Baseline in Vibration Perception Threshold (VPT) Index Finger, Cycle 4 (Day 1)	0.67 Vibration units (vu) Standard Deviation 1.218	-0.14 Vibration units (vu) Standard Deviation 1.588
Change From Baseline in Vibration Perception Threshold (VPT) Index Finger, Cycle 5 (Day 1)	0.93 Vibration units (vu) Standard Deviation 1.291	0.10 Vibration units (vu) Standard Deviation 1.828
Change From Baseline in Vibration Perception Threshold (VPT) Index Finger, Cycle 6 (Day 1)	1.86 Vibration units (vu) Standard Deviation 2.515	-0.07 Vibration units (vu) Standard Deviation 2.213
Change From Baseline in Vibration Perception Threshold (VPT) Index Finger, Cycle 9 (Day 1)	1.94 Vibration units (vu) Standard Deviation 2.221	0.35 Vibration units (vu) Standard Deviation 1.144
Change From Baseline in Vibration Perception Threshold (VPT) Index Finger, Cycle 12 (Day 1)	0.50 Vibration units (vu) Standard Deviation 0.816	0.65 Vibration units (vu) Standard Deviation 0.354
Change From Baseline in Vibration Perception Threshold (VPT) Index Finger, Cycle 15 (Day 1)	0.90 Vibration units (vu) Standard Deviation 0.906	1.30 Vibration units (vu) Standard Deviation NA As only one participant was available here, so standard deviation could not be calculated.
Change From Baseline in Vibration Perception Threshold (VPT) Index finger, End of Treatment	1.23 Vibration units (vu) Standard Deviation 2.108	0.35 Vibration units (vu) Standard Deviation 1.388
Change From Baseline in Vibration Perception Threshold (VPT) Index finger, Post-treatment follow-up	1.34 Vibration units (vu) Standard Deviation 1.727	0.58 Vibration units (vu) Standard Deviation 0.991
Change From Baseline in Vibration Perception Threshold (VPT) Index finger, Worst post-baseline result	1.95 Vibration units (vu) Standard Deviation 2.491	0.67 Vibration units (vu) Standard Deviation 1.721
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, Baseline	5.22 Vibration units (vu) Standard Deviation 2.393	6.60 Vibration units (vu) Standard Deviation 3.525
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, Cycle 2 (Day 1)	0.15 Vibration units (vu) Standard Deviation 1.760	0.08 Vibration units (vu) Standard Deviation 1.988
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, Cycle 3 (Day 1)	0.49 Vibration units (vu) Standard Deviation 2.110	0.20 Vibration units (vu) Standard Deviation 2.589
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, Cycle 4 (Day 1)	0.89 Vibration units (vu) Standard Deviation 2.037	0.82 Vibration units (vu) Standard Deviation 3.679
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, Cycle 5 (Day 1)	1.08 Vibration units (vu) Standard Deviation 1.899	0.54 Vibration units (vu) Standard Deviation 3.645
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, Cycle 6 (Day 1)	2.28 Vibration units (vu) Standard Deviation 2.873	0.39 Vibration units (vu) Standard Deviation 3.371
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, Cycle 9 (Day 1)	2.69 Vibration units (vu) Standard Deviation 3.711	1.34 Vibration units (vu) Standard Deviation 2.417
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, Cycle 12 (Day 1)	1.23 Vibration units (vu) Standard Deviation 2.992	5.35 Vibration units (vu) Standard Deviation 0.636
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, Cycle 15 (Day 1)	1.12 Vibration units (vu) Standard Deviation 3.070	3.40 Vibration units (vu)
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, End of treatment	1.39 Vibration units (vu) Standard Deviation 2.208	1.71 Vibration units (vu) Standard Deviation 2.682
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, Post-treatment follow-up	3.34 Vibration units (vu) Standard Deviation 2.422	1.53 Vibration units (vu) Standard Deviation 3.371
Change From Baseline in Vibration Perception Threshold (VPT) Great toe, Worst post-baseline results	2.39 Vibration units (vu) Standard Deviation 2.762	2.16 Vibration units (vu) Standard Deviation 2.916