FDA Approves HALAVEN® for Advanced Liposarcoma

SUMMARY: The FDA on January 28, 2016, approved HALAVEN® (Eribulin) for the treatment of patients with unresectable or metastatic Liposarcoma, who have received a prior Anthracycline-containing regimen. The American Cancer Society's estimates that in the United States, approximately 11,930 new Soft Tissue Sarcomas were diagnosed in 2015 and 4,870 patients died of the disease. The most common types of sarcoma in adults are, Undifferentiated Pleomorphic Sarcoma ( Malignant Fibrous Histiocytoma), Liposarcoma, and Leiomyosarcoma. Leiomyosarcomas often present as abdominal sarcomas, whereas Liposarcomas and Undifferentiated Pleomorphic Sarcomas develop in the extremities. There are close to 50 different types of Soft Tissue Sarcomas. Liposarcomas are malignant tumors of the adipose tissue.

The approval of HALAVEN® was based on an open-label, randomized, multicenter, phase III trial in which 446 patients with unresectable, locally advanced or metastatic Liposarcoma or Leiomyosarcoma were randomly assigned in a 1:1 ratio to receive either HALAVEN® (N=225) or Dacarbazine (N=221). Eligible patients had received at least two prior systemic chemotherapies (one of which must have included an Anthracycline) and had disease progression within 6 months of randomization. Randomized patients received either HALAVEN® 1.4 mg/m2 on days 1 and 8 of a 21-day cycle or Dacarbazine 850 mg/m2, 1000 mg/m2, or 1200 mg/m2 chosen by the investigator prior to randomization, on day 1 of a 21-day treatment cycle. Treatment was continued until disease progression or unacceptable toxicity. Patients were stratified by histology (Liposarcoma vs. Leiomyosarcoma) and 68% (N=303) had Leiomyosarcoma and 32% (N=143) had Liposarcoma. Majority of the patients had received more than two prior systemic chemotherapies. The median age was 56 years. The primary endpoint of this study was Overall Survival and secondary endpoints included Progression Free Survival and Safety.

The trial met its primary endpoint with a statistically significant improvement in Overall Survival (OS) in the HALAVEN® group compared to the Dacarbazine group. The median OS was 13.5 months in the HALAVEN® arm and 11.3 months in the Dacarbazine arm (HR=0.75; P=0.011). There was no improvement noted in the Progression Free Survival (PFS) or Objective Response Rates in the overall study population. In the pre-planned, exploratory subgroup analyses of OS and PFS, the benefit with HALAVEN® treatment was limited to the subgroup of patients with Liposarcoma (N=143), with a median OS of 15.6 versus 8.4 months for the Dacarbazine group (HR=0.51). There was no treatment benefit with HALAVEN® compared to Dacarbazine treatment, for patients with Leiomyosarcoma (median OS of 12.8 vs 12.3 months; HR=0.90 and median PFS of 2.2 vs 2.6 months; HR=1.05).

The most common adverse reactions associated with HALAVEN® treatment were fever, fatigue, nausea, alopecia, constipation, peripheral neuropathy and neutropenia. Thrombocytopenia was more frequent in the Dacarbazine group than HALAVEN® group. It was concluded that HALAVEN® significantly improves Overall Survival in patients with advanced, pretreated Liposarcoma and is the first drug approved for this patient population. Schöffski P, Maki RG, Italiano A, et al. Randomized, open-label, multicenter, phase III study of eribulin versus dacarbazine in patients (pts) with leiomyosarcoma (LMS) and adipocytic sarcoma (ADI). J Clin Oncol. 2015;(suppl; abstr LBA10502).