The European Commission has approved eribulin mesylate (Halaven) as a treatment for patients with advanced or unresectable liposarcoma following anthracycline-based chemotherapy.
Patrick Schöffski, MD
The European Commission has approved eribulin mesylate (Halaven) as a treatment for patients with advanced or unresectable liposarcoma following anthracycline-based chemotherapy, based on data from the pivotal phase III trial, Study 309.
In the trial, the microtubule dynamics inhibitor eribulin demonstrated a median overall survival (OS) of 15.6 months compared with 8.4 months in patients who received dacarbazine (HR = 0.511; 95% CI, 0.346-0.753; P = .0006) 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).
“This decision marks an important milestone for people in Europe with advanced liposarcomas. There are currently limited treatment options available, but now, we are a step closer to being able to offer them a treatment with a proven overall survival benefit. Eribulin was the first-ever single-agent therapy to show such a survival benefit, which makes today's news all the more important for patients and clinicians across Europe," Patrick Schöffski, MD, University Hospitals Leuven, Belgium, said in a statement.
In Study 309, 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 11.5 months for dacarbazine, representing a >23% reduction in the risk of death (HR, 0.768; 95% CI 0.618-0.954; P = .017). Median PFS was 2.6 months in both arms of the study across the full population (HR = 0.877; 95% CI, 0.710-1.085; P = .229). 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).
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.
"At Eisai, our first thought is with people in Europe who now have access to this new treatment and the benefit it may have for them and their families. This is the second form of cancer in which eribulin has demonstrated an overall survival benefit when compared to active therapy. We are encouraged by the Commission's decision, and will continue with our commitment to develop and discover products that have a positive impact on patients and their families,” Gary Hendler, chief commercial officer, Oncology Business Group, Chairman and CEO EMEA at Eisai, the manufacturer of eribulin, said in a statement.
Schöffski P, Chawla S, Maki RG, et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016;387(10028):1629-1637.