Abstract P6-14-05: 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 , Irwin A , Jensen L , Tedesco K , Misir S , Zhu W , Almonte A , He Y , Olivo M , O'Shaughnessy J 
Published: February 2018

Abstract
Background: Eribulin mesylate, a microtubule inhibitor, is approved in the US 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 day (D) 1 and D8 of a 21-D cycle. However, this schedule can result in dose delays and reductions due to myelosuppression. A dosing regimen of eribulin (1.4 mg/m2) administered intravenously (IV) biweekly (Q2W; on D1 and D15) in 28-D cycles was evaluated with the intent of improving eribulin's safety profile without compromising efficacy.
Methods: Female pts with human epidermal growth factor receptor (HER)2-negative MBC, who had received 2-5 prior chemotherapy regimens and had ECOG PS ≤2 were enrolled in 12 sites in the US. Prophylactic granulocyte colony-stimulating factor (G-CSF) was not allowed. If neutropenia occurred, growth factors were used during eribulin treatment at the physician's discretion. Primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), dose intensity (measured by feasibility rate), safety and tolerability.
Results: Median age of the 58 enrolled pts was 64 yrs (range: 38-85). The majority of pts (93%) had ECOG PS ≤1, and 12% of pts had triple-negative MBC. Number of prior chemotherapeutic regimens: 2 (17% of patients), 3 (24%), 4 (27%), and 5 (31%). 76% Of pts had visceral disease and 86% had previous taxane therapy. ORR (95% confidence interval [CI]) was 12% (5-24), DCR (CR+PR+SD) was 65% (95% CI: 51-77), and CBR (CR+PR+SD ≥23 weeks) was 30% (95% CI: 18-43) [n=57]. Median PFS (95% CI) was 3.6 mo (2.9-4.1). Median OS (95% CI) was 13.2 mo (10.6-not estimable). 6-Month and 12-month OS rates were 84% and 54%, respectively. Dose intensity measured by the feasibility rate (defined as the percentage of pts completing the first 2 and 4 cycles without a dose delay &gt;5 days or dose reduction due to an adverse event [AE]) was 70% and 46%, respectively.
The most frequent AEs (all grades) were neutropenia (69%), fatigue (48%), alopecia (45%), and constipation (36%). 22% Of pts had grade (G) 1 alopecia and 22% of pts had G2 alopecia. 72% Of pts had G3/4 AEs: neutropenia, 57%, and peripheral neuropathy, 12%. G3 peripheral sensory neuropathy occurred in 9% of pts, with no G4 incidence. There were 2 deaths (1 sepsis, 1 acute respiratory failure), which were considered not related to treatment. 50% (29/58) Of all patients received at least 1 dose of growth factor and 70% (28/40) of patients with neutropenia received growth-factor support.
Conclusions: Tumor response rates and OS of this treatment schedule in a heavily pretreated patient population were similar compared to previously reported phase 3 studies of eribulin. The toxicities associated with biweekly eribulin were manageable.
Citation Format: Smith II J, Irwin A, Jensen L, Tedesco K, Misir S, Zhu W, Almonte A, He Y, Olivo M, O'Shaughnessy J. 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 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-14-05.