FDA Approves Eribulin for Advanced Liposarcoma

Richard Pazdur, MD

The FDA has approved eribulin mesylate (Halaven) as a treatment for patients with advanced or unresectable liposarcoma following prior treatment with an anthracycline-based chemotherapy, based on an improvement in overall survival (OS) in a phase III study.

In 143 patients with liposarcoma, the microtubule dynamics inhibitor eribulin demonstrated a median OS of 15.6 months compared with 8.4 months in those who received dacarbazine (HR, 0.51; 95% CI, 0.35-0.75). Median progression-free survival (PFS) with eribulin was 2.9 versus 1.7 months with dacarbazine (HR, 0.52; 95% CI, 0.35-0.78).

“Halaven is the first drug approved for patients with liposarcoma that has demonstrated an improvement in survival time,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “The clinical trial data the FDA reviewed indicates that Halaven increased overall survival by approximately seven months, offering patients a clinically meaningful drug.”

In the pivotal phase III study, which was presented at the 2015 ASCO Annual Meeting, 452 patients with advanced soft tissue sarcoma were randomized to receive eribulin (n = 228) or dacarbazine (n = 224). Eribulin was administered at 1.4 mg/m² on days 1 and 8 and dacarbazine was administered at 850, 1000, or 1200 mg/m² on day 1 of each 21-day cycle.

Patients enrolled had high- or intermediate-grade sarcoma and the majority had received 2 or more prior therapies. Overall, 143 patients had liposarcoma and 309 had leiomyosarcoma. The primary endpoint of the study was OS, with secondary outcomes focused on PFS and safety.

Across the full study, median OS with eribulin was 13.5 months compared with 11.3 months for dacarbazine, representing a 25% reduction in the risk of death (HR, 0.75; 95% CI, 0.61-0.94; P = .011). Median PFS was 2.6 months in both arms of the study across the full population (HR, 0.88; 95% CI, 0.71-1.09; P = .2287). The 12-week PFS rate was 33% with eribulin and 28.6% with dacarbazine; however, this difference was not deemed statistically significant (odds ratio = 1.3; P = .253).

The objective response rate (all partial responses) was 3.9% with eribulin versus 4.9% with dacarbazine. The stable disease rate with eribulin was 52.2% compared with 47.8% with dacarbazine.

In patients with leiomyosarcoma, outcomes were similar between the two arms. Median OS was 12.8 months with eribulin versus 12.3 months with dacarbazine (HR, 0.90; 95% CI, 0.69-1.18). Median PFS was 2.2 versus 2.6 months, in the eribulin and dacarbazine arms, respectively (HR, 1.05; 95% CI, 0.81-1.35).

"There is an unmet medical need for patients with soft tissue sarcoma whose disease no longer responds to treatment," George Demetri, MD, Professor of Medicine at Harvard Medical School and Director of the Center for Sarcoma and Bone Oncology at Dana-Farber Cancer Institute, said in a statement. "Halaven has been shown to help patients with advanced liposarcoma live longer, a meaningful result for patients with this rare and hard-to-treat disease."

All-grade adverse events (AEs) were seen in almost all patients in the study. The most common AEs in the eribulin arm were neutropenia (43.8%), fatigue (43.8%), nausea (40.3%), alopecia (35%), and constipation (31.4%). With dacarbazine, the most common AEs were nausea (47.3%), fatigue (38.4%), anemia (30.8%), thrombocytopenia (27.7%), and constipation (25.9%).

Grade ≥3 treatment-related AEs were reported in 67.3% of patients treated with eribulin compared with 56.3% with dacarbazine. The most common grade ≥3 AEs with eribulin were neutropenia (35.4%) and anemia (7.1%) versus neutropenia (15.6%), anemia (12.1%), and thrombocytopenia (15.2%).

The FDA initially approved eribulin in 2010 for the treatment of patients with metastatic breast cancer. This approval was based on a 2.5-month extension in OS experienced by patients treated with eribulin compared with physician's choice of treatment in the phase III EMBRACE trial. The treatment continues to be assessed in clinical trials across a variety of settings.

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).