A phase III study (EMBRACE) of eribulin mesylate versus treatment of physician's choice in patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane.

CRA1004^ Background: Eribulin mesylate (E7389; E) is a nontaxane microtubule dynamics inhibitor with a novel mode of action. This study is the first to compare overall survival (OS) with this new chemotherapeutic (CT) agent to real-life choices in heavily pretreated patients (pts) with metastatic breast cancer (MBC). METHODS Women with locally recurrent or MBC were enrolled in this phase III open-label, randomized, multicenter study. Pts had received 2-5 prior CT (≥2 for advanced disease), including an anthracycline and a taxane, unless contraindicated. Pts were randomized 2:1 to E 1.4 mg/m2 2-5 min IV bolus on days 1 and 8 of a 21-day cycle or treatment of physician's choice (TPC). TPC was any monotherapy (cytotoxic, hormonal, biologic) or supportive care only. The primary endpoint was OS; secondary endpoints were objective response rate (ORR), and progression-free survival (PFS) by independent review, and duration of response (DOR). Safety and tolerability were assessed. Data are from the final analysis after 422 deaths. RESULTS 762 pts were treated (508 E, 254 TPC). Median age was 55.2 (range 27-85), 16% were HER2-positive, 19% triple-negative, 73% received prior capecitabine, median no. of prior CT was 4. Median OS was 13.1 months (mo) for E vs. 10.7 mo for TPC, p=0.04 (primary analysis, stratified log rank test; HR 0.81; 95% CI 0.66, 0.99). Median PFS was 3.7 mo for E and 2.3 mo for TPC p=0.09 (HR 0.85; 95% CI 0.70, 1.03). ORR was 12% (0.4% complete response [CR], 11.5% partial response [PR]) for E and 5% (0 CR; 5% PR) for TPC, p=0.005. Median DOR was 4.1 mo for E (56 responders) vs. 6.7 mo for TPC (11 responders). Grade [G] 3/4 treatment-related adverse events (AEs) of interest for E were asthenia/fatigue (7.6%), neutropenia (44%), peripheral neuropathy (8.4%). 10% of pts experienced treatment-related serious AEs (12% E, 7% TPC). CONCLUSIONS The study met its primary endpoint with a significant improvement in OS by a median of 2.5 mo with E vs. TPC. E demonstrated a manageable tolerability profile, acceptable for a CT agent used as monotherapy in this late-line setting. [Table: see text] In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco. org/conflictofinterest .