Eribulin mesylate (Halaven) has received a positive recommendation from the EMA’s Committee for Medicinal Products for Human Use (CHMP) as a treatment for patients with advanced or unresectable liposarcoma following prior treatment with an anthracycline-based chemotherapy.
The positive opinion suggests the microtubule dynamics inhibitor eribulin is likely to be approved when the European Commission issues its final decision.
The CHMP based its recommendation on data from a pivotal phase III trial, Study 309, in which eribulin demonstrated a median overall survival (OS) of 15.6 months compared with 8.4 months in received dacarbazine (HR, 0.51; 95% CI, 0.35-0.75) in a cohort of 143 patients with liposarcoma. Median progression-free survival (PFS) in the group was 2.9 months with eribulin versus 1.7 months with dacarbazine (HR, 0.52; 95% CI, 0.35-0.78).
In Study 309, 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
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).
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 approved eribulin in January 2016 as a treatment for patients with advanced or unresectable liposarcoma following prior treatment with an anthracycline-based chemotherapy. In February 2016, eribulin was approved in Japan for the treatment of patients with soft tissue sarcoma.
“Through obtaining this additional approval, Eisai aims to enhance the clinical value of Halaven to contribute further toward addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers,” Eisai, the manufacturer of eribulin, said in a statement.
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).