Primary Outcomes

Description: The patient-reported maximum score (post baseline) across Patient Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) items for each patient will be computed over the first 12 weeks and compared between arms using a two-sample independent samples t-test.

Measure: Patient-reported maximum score

Time: Up to 12 weeks after treatment initiation

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Description: The Cox score test will be used to test the association between the cumulative dose level triggering toxicity and the genotype. The goal is to validate the EPHA5 rs7349683 single neucleotide polymorphism (SNP).

Measure: Validation of germline EPHA5 polymorphism (rs7349683)

Time: Up to 5 years

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Secondary Outcomes

Description: The primary analysis will use the stratified log-rank tests, as described for overall survival. As a secondary analysis we will use a multivariable Cox proportional hazard model to estimate adjusted hazard ratios for eribulin mesylate over standard weekly paclitaxel, study stratification factors, and covariates for known prognostic factors, including disease free interval and visceral versus non-visceral metastases. Survival functions will be summarized using the Kaplan-Meier method according to treatment group.

Measure: Overall survival (OS)

Time: From randomization to death due to any cause, assessed up to 5 years

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Description: The primary analysis will use the Cochran-Mantel-Haenszel chi-squared test with study stratification factors. Secondary analyses will use logistic regression to test differences in proportions while controlling for the covariates. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Objective tumor response assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Time: Up to 5 years

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Description: Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Duration of response

Time: Up to 5 years

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Description: Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Time to treatment failure

Time: Up to

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Description: The primary analysis will use the Cochran-Mantel-Haenszel chi-squared test with study stratification factors. Secondary analyses will use logistic regression to test differences in proportions while controlling for the covariates. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Incidence of treatment related adverse events

Time: Up to 30 days after last dose assessed by CTCAE version 4.0

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Description: Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Time to new metastasis

Time: Up to 5 years

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Description: Will be summarized using the Kaplan-Meier method. Will use a two-sided type I alpha of 0.05, and point estimates will be reported with 95% confidence intervals.

Measure: Progression free survival assessed by RECIST 1.1 criteria

Time: From randomization to progression or death due to any cause, whichever occurs first, assessed up to 5 years

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Description: Additional analyses will include the previously described analysis conducted over the first 24 weeks; a comparison of the incidence of patient-reported maximum score >= 3 between arms through 12 and 24 weeks using chi-squared testing for each item; and a comparison of the time to patient-reported score >= 3 between arms using Kaplan-Meier and log-rank analyses. Further, these three endpoints will be compared between patient- and clinician-report overall and within arms using appropriate paired analyses.

Measure: Patient reported neurotoxicity

Time: Up to 24 weeks

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Description: The PRO-CTCAE sensory neuropathy items will be further validated by computing Pearson correlations between each item and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20 )sensory scale score at baseline, 12 and 24 weeks.

Measure: Validation of PRO-CTCAE sensory neuropathy item

Time: At baseline, 12 and 24 weeks

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Other Outcomes

Description: Will be summarized using the Kaplan-Meier method according to treatment group.

Measure: New metastasis free survival

Time: Up to 5 years

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