Abstract OT3-02-11: Phase 2 study evaluating the efficacy and safety of eribulin mesylate administered biweekly for patients with human epidermal growth factor receptor 2-negative metastatic breast cancer
Authors: Smith J , O'Shaughnessy J , Song J , Berrak E 
Published: May 2016

Abstract
Eribulin mesylate, a mitotic inhibitor, is indicated for the treatment of patients (pts) with metastatic breast cancer (MBC) who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease, including an anthracycline and a taxane. The recommended dose is 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin [expressed as free base]) on d1 and 8 of a 21d cycle. A modified biweekly dose regimen—which may improve safety profile without compromising efficacy—is also being explored.
This presentation describes an ongoing phase 2, open-label, single-arm, multicenter study of eribulin (1.4 mg/m2) administered intravenously (IV) biweekly (d1 and 15) in 28d cycles for the treatment of pts with human epidermal growth factor receptor (HER)2-negative MBC previously treated with 2–5 chemotherapy regimens.
Approximately 58 female pts (aged ≥18 yrs) will be enrolled to have 55 evaluable pts; accrual has not yet commenced. Pts with ≥1 measurable lesion ≥10 mm in longest diameter (nonlymph node) or ≥15 mm in short-axis diameter (lymph node) with an Eastern Cooperative Oncology Group performance status ≤2 and life expectancy ≥3 months will be included. Exclusion criteria include treatment with chemotherapy, radiation, biological, or targeted therapy within the last 2 weeks (or 5 × half-life); existing anticancer-therapy–related toxicities of grades ≥2 (except alopecia); and prior malignancy other than carcinoma in situ of the cervix or nonmelanoma skin cancer (unless prior malignancy was treated &gt;5 yrs ago with no evidence of recurrence). Pts will receive treatment as long as clinical benefit is demonstrated or until intercurrent illness, unacceptable toxicity, or disease progression.
The study consists of 3 phases: a screening phase, treatment phase (estimated median treatment duration 5 months), and posttreatment survival follow-up phase. The study is divided into 2 stages (Simon 2-stage design): stage 1 (n=15 evaluable pts who have completed 3 cycles of treatment) allows for an interim analysis of efficacy results to end the trial early in the case of low anticancer activity (&lt;1 responder [objective response rate; ORR] and &lt;8 responders [disease control rate; DCR]). Otherwise, the study will proceed to Stage 2 (40 evaluable pts). Final analysis will take place after all ongoing pts complete ≥5 cycles of treatment or discontinue from treatment and ≥75% pts experience disease progression or death.
The primary objective is to evaluate efficacy in terms of ORR and DCR. A modified Simon 2-Stage Design will be used in hypothesis testing for these endpoints as well as the stage 1 interim futility analysis. Secondary objectives include evaluation of progression-free survival (PFS), overall survival (OS), safety, and tolerability. PFS and OS will be analyzed using Kaplan–Meier product-limit estimates. Median PFS, OS, and cumulative probability of PFS and OS at 3, 6, and 12 months will be calculated with 2-sided 95% confidence intervals, if estimable. The final analysis thresholds for success are defined as ≥7 responders by ORR or ≥32 responders by DCR out of 55 evaluable pts.
Citation Format: Smith J, O'Shaughnessy J, Song J, Berrak E. Phase 2 study evaluating the efficacy and safety of eribulin mesylate administered biweekly for patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-02-11.