FDA Approval for Eribulin Mesylate
Brand name(s): Halaven™
- Approved for treatment of metastatic breast cancer after at least two treatment regimens with an anthracycline and a taxane.
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications.
On November 15, 2010, the Food and Drug Administration (FDA) granted approval for eribulin mesylate (Halaven™ Injection, made by 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 III international multicenter open-label randomized clinical trial, Study E7389-G000-305 (EMBRACE trial). This trial demonstrated a statistically significant improvement in overall survival (OS) in patients receiving eribulin compared with 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 randomly assigned (2:1) to receive eribulin (n=508) or a single-agent therapy selected by their physician (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. Therapy in the control group consisted of vinorelbine (26 percent),gemcitabine (18 percent), capecitabine (18 percent), taxane (16 percent), anthracycline (9 percent), other chemotherapy (10 percent), or hormonal therapy (3 percent).
Patient demographic and baseline characteristics were comparable between the treatment groups. The median age was 55 (range: 27 to 85 years). Sixty-four percent of patients were enrolled in North America/Western Europe/Australia, 25 percent in Eastern Europe/Russia, and 11 percent 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 percent, negative: 28 percent), progesterone receptor status (positive: 49 percent, negative: 39 percent), HER2/neu receptor status (positive: 16 percent, negative: 74 percent), triple-negative status (ER, PR, HER2/neu:19 percent), presence of visceral disease (82 percent) and bone disease (61 percent), and number of sites of metastases (greater than two: 50 percent). These characteristics were also similar in the eribulin and control groups. Both groups of patients had received a median of four prior chemotherapy regimens.
A statistically significant prolongation in OS was observed in patients treated with eribulin. Median OS was 13.1 months (95 percent CI: 11.8, 14.3) for patients treated with eribulin versus 10.6 months (95 percent CI: 9.3, 12.5) for patients in the control group [HR 0.809 (95 percent CI: 0.660, 0.991), p=0.041].In patients treated with eribulin, the objective response rate by the RECIST criteria was 11 percent (95 percent CI: 8.6 percent, 14.3 percent) and the median response duration was 4.2 months (95 percent CI: 3.8, 5.0 months).
The most common adverse reactions (in at least 25 percent of patients) associated with eribulin were neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, and constipation. The most common grade 3 and above adverse reactions (more than 5 percent) related to eribulin were neutropenia (57 percent), asthenia/fatigue (10 percent), and peripheral neuropathy (8 percent). The most common serious adverse reactions reported in patients treated with eribulin were febrile neutropenia (4 percent) and neutropenia (2 percent). Peripheral neuropathy was the most common toxicity leading to discontinuation of eribulin (5 percent).
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.