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U.S. Department of Health and Human Services

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Eribulin Mesylate

On 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).