FDA Grants Priority Review to Eribulin for Soft Tissue Sarcoma

Kenichi Nomoto, PhD

The FDA has granted a priority review designation to eribulin mesylate (Halaven) as a treatment for patients with advanced soft tissue sarcoma following chemotherapy, according to a statement from the drug's developer, Eisai.

The application for eribulin was based on an extension in overall survival (OS) with the microtubule dynamics inhibitor compared with dacarbazine in the phase III Study 309 trial. In the study, pretreated patients with intermediate- and high-grade leiomyosarcoma (LMS) or adipocytic sarcoma (ADI) experienced a median OS with eribulin of 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).

Findings from the open-label Study 309 trial were presented at the 2015 ASCO Annual Meeting, and represented the first phase III study to show an OS improvement for patients with soft tissue sarcoma. Under the Prescription Drug User Fee Act, the FDA is scheduled to make a decision on the application before March 30, 2016.

"Advanced soft tissue sarcoma is very difficult to treat, so we are excited to be one step closer to potentially bringing an additional treatment option to patients in need," Kenichi Nomoto, PhD, president, Oncology Product Creation Unit at Eisai, said in a statement.

In the 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. The primary endpoint of the study was OS, with secondary outcomes focused on progression-free survival (PFS) and safety.

The median OS in patients with the ADI subtype was 15.6 months with eribulin (n = 75) compared with 8.4 months with dacarbazine (n = 78; HR, 0.51; 95% CI, 0.35-0.75). In the LMS group, patients treated with eribulin (n = 152) had a median OS of 12.7 versus 13 months with dacarbazine (n = 145; HR, 0.93; 95% CI, 0.71-1.20).

"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."

Median PFS was 2.6 months in both arms of the study (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.

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%).

"We looked at the safety profile of the drugs that we used in this trial and we found that the safety findings matched our experience with these two drugs in other settings of oncology," Schöffski said. "There were no new safety findings. There were only two treatment-related deaths in this study, both occurring in the eribulin arm."

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).