ERIBULIN FOR BREAST CANCER

J Clin Oncol. 2010 Aug 2. [Epub ahead of print]
Phase II Study of the Halichondrin B Analog Eribulin Mesylate in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline, a Taxane, and Capecitabine.
Cortes J, Vahdat L, Blum JL, Twelves C, Campone M, Roché H, Bachelot T, Awada A, Paridaens R, Goncalves A, Shuster DE, Wanders J, Fang F, Gurnani R, Richmond E, Cole PE, Ashworth S, Allison MA.

Vall d'Hebron University Hospital, Barcelona, Spain; Weill Cornell Medical College, New York, NY; Baylor-Charles A. Sammons Cancer Center; Texas Oncology PA; US Oncology, Dallas; US Oncology, Houston, TX; Eisai Medical Research, Woodcliff Lake, NJ; Comprehensive Cancer Centers of Nevada, Henderson, NV; Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds; Eisai, London, United Kingdom; Centre de Lutte Contre le Cancer René Gauducheau, Nantes; Institut Claudius Régaud, Toulouse; Centre Léon Bérard, Lyon; Institut Paoli Calmettes, Marseille, France; Institut Jules Bordet, Université Libre de Bruxelles, Brussels; and University Hospital Gasthuisberg, Leuven, Belgium.
Abstract

PURPOSE The activity and safety of eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor with a novel mechanism of action, were evaluated in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, taxane, and capecitabine. PATIENTS AND METHODS Eligible patients in this single-arm, open-label phase II study received eribulin mesylate (1.4 mg/m(2)) administered as a 2- to 5-minute intravenous infusion on days 1 and 8 of a 21-day cycle. The primary end point was objective response rate (ORR) assessed by independent review. Results Of 299 enrolled patients who had received a median of four prior chemotherapy regimens, 291 received eribulin (for a median of four cycles). Of these, 269 patients met key inclusion criteria for the primary efficacy analysis. The primary end point of ORR by independent review was 9.3% (95% CI, 6.1% to 13.4%; all partial responses [PRs]), the stable disease (SD) rate was 46.5%, and clinical benefit rate (complete response + PR + SD >/= 6 months) was 17.1%. The investigator-reported ORR was 14.1% (95% CI, 10.2% to 18.9%). Median duration of response was 4.1 months, and progression-free survival was 2.6 months. Median overall survival was 10.4 months. The most common treatment-related grade 3 or 4 toxicities were neutropenia (54%; febrile neutropenia, 5.5%), leukopenia (14%), and asthenia/fatigue (10%; no grade 4); grade 3 neuropathy occurred in 6.9% of patients (no grade 4). CONCLUSION Eribulin demonstrated antitumor activity in extensively pretreated patients who had previously received an anthracycline, taxane, and capecitabine, with a manageable tolerability profile.