FDA Approves Eribulin Mesylate in Unresectable or Metastatic Liposarcoma
The U.S. Food and Drug Administration today approved eribulin mesylate (Halaven), an antimicrotubular antineoplastic agent, for the treatment of unresectable or metastatic liposarcoma. This treatment is approved for patients who received prior chemotherapy that contained an anthracycline drug.
“Eribulin mesylate is the first drug approved for patients with liposarcoma that has demonstrated an improvement in survival time,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The clinical trial data the FDA reviewed indicates that eribulin mesylate increased overall survival by approximately 7 months, offering patients a clinically meaningful drug.”
Soft-tissue sarcoma is a disease in which cancer cells form in the soft tissues of the body, including the muscles, tendons, fat, blood vessels, lymph vessels, nerves, and tissues around joints. Liposarcoma is a specific type of soft-tissue sarcoma that occurs in fat cells. Soft-tissue sarcoma can form almost anywhere in the body, but is most common in the head, neck, arms, legs, trunk, and abdomen. In 2014, an estimated 12,000 cases of soft-tissue sarcoma were diagnosed in the United States, according to the National Cancer Institute.
Clinical Trial Background
The approval was based on an open-label, randomized, multicenter, active-controlled trial in 446 patients with unresectable, locally advanced, or metastatic liposarcoma or leiomyosarcoma who had received at least two prior systemic chemotherapies (one of which must have included an anthracycline) and had experienced disease progression within 6 months of randomization. Patients were randomized to receive either eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day cycle, or dacarbazine (at a dose of 850 mg/m2, 1000 mg/m2, or 1200 mg/m2 chosen by the investigator prior to randomization) on day 1 of a 21-day cycle. Treatment was continued until disease progression or unacceptable toxicity. Patients were stratified by histology (liposarcoma vs leiomyosarcoma), number of prior therapies (2 vs greater than 2), and geographic region. Patients on the dacarbazine arm were not offered eribulin at the time of progression.
A total of 446 patients were randomized, 225 to eribulin and 221 to dacarbazine. The median age was 56 years (range: 24–83); 33% were male; 73% were white; 44% had ECOG performance status (PS) 0 and 53% had ECOG PS 1; 68% had leiomyosarcoma and 32% had liposarcoma; and 47% received more than two prior systemic chemotherapies.
Clinical Trial Results
The trial met its primary endpoint based on demonstration of a statistically significant improvement in overall survival (OS) in the eribulin arm compared to the dacarbazine arm with a hazard ratio (HR) of 0.75 (95% CI: 0.61, 0.94; p=0.011). The median OS was 13.5 months in the eribulin arm and 11.3 months in the dacarbazine arm. There was no improvement in progression-free survival (PFS) or confirmed objective response rates in the overall study population.
Treatment effects of eribulin were limited to the stratified subgroup of patients with liposarcoma, observed in preplanned, exploratory subgroup analyses of OS and PFS. The median OS was 15.6 vs 8.4 months [HR 0.51 (95% CI: 0.35, 0.75)] and the median PFS was 2.9 vs 1.7 months [HR 0.52 (95% CI: 0.35, 0.78)] in patients with liposarcoma treated with eribulin compared to dacarbazine, respectively. There was no evidence of efficacy for eribulin in patients with leiomyosarcoma: median OS of 12.8 vs 12.3 months [HR 0.90 (95% CI: 0.69, 1.18)] and median PFS of 2.2 vs 2.6 months [HR 1.05 (95% CI: 0.81, 1.35)] in patients with treated with eribulin compared to dacarbazine, respectively.
Safety was evaluated in the 223 patients with liposarcoma and leiomyosarcoma who received eribulin in the trial. The most common (greater than or equal to 25%) adverse reactions were fatigue, nausea, alopecia, constipation, peripheral neuropathy, abdominal pain, and pyrexia. The most common (greater than or equal to 5%) grade 3–4 laboratory abnormalities were neutropenia, hypokalemia, and hypocalcemia.
The most common serious adverse reactions were neutropenia (4.9%) and pyrexia (4.5%). Febrile neutropenia occurred in 0.9% and fatal neutropenic sepsis in 0.9% of patients treated with eribulin. The most frequent adverse reactions leading to discontinuation were fatigue (0.9%) and thrombocytopenia (0.9%).
The recommended dose and schedule for eribulin is 1.4 mg/m2 on days 1 and 8 of a 21-day cycle.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
