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.
Richard Pazdur, MD
Eribulin mesylate (Halaven) has been approved by the FDA for patients with advanced or unresectable liposarcoma, following anthracycline-based chemotherapy treatment. The approval was based on overall survival (OS) improvement in an open-label phase III study.
In a subpopulation of 143 patients with liposarcoma participating in the study, the microtubule dynamics inhibitor eribulin demonstrated a median OS of 15.6 months. This is compared with 8.4 months OS in those who received dacarbazine (HR, 0.51; 95% CI, 0.35-0.75). These findings mark the first time an agent has shown a survival benefit for patients with liposarcoma, according to the FDA.
"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, FDA 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."
Findings from the phase III trial were presented at the 2015 ASCO Annual Meeting. Under the Prescription Drug User Fee Act, the FDA was scheduled to make a decision on the application by March 30, 2016, placing their decision approximately 2 months ahead of deadline.
In the pivotal phase III study, 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 progression-free survival (PFS) and safety.
Across the full study, median OS with eribulin was 13.5 months compared with 11.5 months for dacarbazine, representing a 23% reduction in the risk of death (HR, 0.77; 95% CI, 0.62-0.95;P= .0169). In patients with leiomyosarcoma, median OS was 12.7 months with eribulin versus 13 months with dacarbazine (n = 145; HR, 0.93; 95% CI, 0.71-1.20).
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.
"This is the very first phase III trial investigating patients with soft tissue sarcoma to demonstrate an overall survival benefit of a new agent compared with an active agent," lead investigator Patrick Schöffski, MD, MPH, head of Department of General Medical Oncology, University Hospitals Leuven in Leuven, Belgium, said when the data were presented. "This is a clinically meaningful result given the high unmet medical need in this rare, hard-to-treat family of diseases."
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.