Positive results from a pivotal phase III study investigating the use of eribulin mesylate injection (Halaven, Eisai, Inc.) in certain types of soft-tissue sarcoma have been published online in the Lancet. The study evaluated overall survival (OS, the primary endpoint) in previously treated patients with advanced liposarcoma or leiomyosarcoma treated with eribulin compared with those treated with dacarbazine.
Based on the significant improvement in OS observed in the preplanned exploratory subgroup analysis of the liposarcoma group, the FDA approved eribulin in January 2016 for the treatment of patients with unresectable or metastatic liposarcoma who have received an anthracycline-containing regimen.
Although soft-tissue sarcomas are relatively rare, they are associated with a poor prognosis, with many patients being unresponsive to treatment. Approximately 12,000 cases of soft-tissue sarcomas are diagnosed in the U.S. each year.
Study 309 was a randomized, open-label, active-controlled trial of eribulin mesylate 1.4 mg/m2 administered intravenously (IV) on days one and eight of a 21-day cycle compared with dacarbazine IV on day one every 21 days (dose range of 850 mg/m2 to 1,200 mg/m2) until disease progression. The study included 446 patients with unresectable, locally advanced or metastatic liposarcoma or leiomyosarcoma who had been treated with at least two systemic chemotherapies, one of which must have included an anthracycline, and who had disease progression within six months of the most recent chemotherapy regimen.
In this study, eribulin demonstrated a significant improvement in OS compared with dacarbazine. Median OS in all treated patients was 13.5 months with eribulin compared with 11.3 months with dacarbazine (hazard ratio, 0.75; P = 0.011). The treatment effects of eribulin were limited to patients with liposarcoma, according to preplanned subgroup analyses of OS.
The most common adverse events observed in patients with liposarcoma or leiomyosarcoma treated with eribulin included fatigue (62%), nausea (41%), alopecia (35%), constipation (32%), peripheral neuropathy (29%), abdominal pain (29%) and pyrexia (28%). The most common serious adverse events in patients receiving eribulin included neutropenia (4.9%) and pyrexia (4.5%). The most common adverse events resulting in the discontinuation of eribulin included fatigue and thrombocytopenia (0.9% each).
First in the halichondrin class, eribulin mesylate is a microtubule dynamics inhibitor with a distinct binding profile. It is a synthetic analog of halichondrin B, a natural product that was isolated from the marine sponge Halichondria okadai. Based on in vitro studies, eribulin exerts its effect via a tubulin-based antimitotic mechanism, ultimately leading to cell apoptosis after prolonged and irreversible mitotic blockade. In addition, the treatment of human breast-cancer cells with eribulin caused changes in cell structure and gene expression as well as decreased migration and invasiveness in vitro.
Source: Eisai; February 10, 2016.