FDA Grants Approval for Eribulin Mesylate
Monday, November 15, 2010
The U.S. Food and Drug Administration granted approval for eribulin mesylate (Halaven™ Injection, Eisai Inc.) for the treatment of patients with metastatic breast cancer who have previously received an anthracycline and a taxane in either the adjuvant or metastatic setting, and at least two chemotherapeutic regimens for the treatment of metastatic disease. Halaven is a non-taxane, microtubule dynamics inhibitor that is a synthetic analogue of halichondrin B, a product isolated from the marine sponge Halichondria okadai.
The approval is based on results from a phase 3, international, multicenter, open-label, randomized clinical trial, Study E7389-G000-305 (EMBRACE trial). This trial demonstrated a statistically significant improvement in overall survival (OS) observed in patients receiving eribulin compared to those receiving a single agent therapy selected by their physician.
In Study E7389-G000-305, a total of 762 patients with metastatic breast cancer were randomized (2:1) to receive eribulin (n=508) or a single agent therapy selected by their physician prior to randomization (control arm, n = 254). Randomization was stratified by geographic region, HER2/neu status, and prior capecitabine exposure. Patients were required to have received at least two chemotherapeutic regimens for the treatment of metastatic disease and to have experienced disease progression within 6 months of their last chemotherapeutic regimen. Patients must have had prior anthracycline- and taxane-based chemotherapy in either the adjuvant or metastatic setting.
Eribulin was administered as an intravenous dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle, with dose delays and reductions for pre-specified toxicities. Control arm therapy consisted of vinorelbine (26%), gemcitabine (18%), capecitabine (18%), taxane (16%), anthracycline (9%), other chemotherapy (10%), or hormonal therapy (3%).
Patient demographic and baseline characteristics were comparable between the treatment arms. The median age was 55 (range: 27 to 85 years). Sixty-four percent of patients were enrolled in North America/Western Europe/Australia, 25% in Eastern Europe/Russia, and 11% in Latin America/South Africa. Ninety-one percent of patients had a baseline ECOG performance status of 0 or 1. Tumor prognostic characteristics included estrogen receptor status (positive: 67%, negative: 28%), progesterone receptor status (positive: 49%, negative: 39%), HER2/neu receptor status (positive: 16%, negative: 74%), triple negative status (ER-, PR-, HER2/neu-: 19%), presence of visceral disease (82%) and bone disease (61%), and number of sites of metastases (greater than two: 50%). These characteristics were also similar in the eribulin and control arms. Patients received a median of four prior chemotherapy regimens in both arms.
A statistically significant prolongation in OS was observed in patients randomized to receive eribulin; median OS was 13.1 months (95% CI: 11.8, 14.3) versus 10.6 months (95% CI: 9.3, 12.5) in the eribulin and control arms, respectively [HR 0.809 (95% CI: 0.660, 0.991), p=0.041]. In patients randomized to receive eribulin, the objective response rate by the RECIST criteria was 11% (95% CI: 8.6%, 14.3%) and the median response duration was 4.2 months (95% CI: 3.8, 5.0 months).
The most common adverse reactions (> 25%) associated with eribulin were neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, and constipation. The most common grade 3 and above adverse reactions (>5%) related to eribulin were neutropenia (57%), asthenia/fatigue (10%), and peripheral neuropathy (8%). The most common serious adverse reactions reported in eribulin-treated patients were febrile neutropenia (4%) and neutropenia (2%). Peripheral neuropathy was the most common toxicity leading to discontinuation of eribulin (5%).
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201532lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).