Eribulin Extends Survival in Phase 3 Sarcoma Study

Treatment with eribulin mesylate significantly extended overall survival (OS) compared with dacarbazine in patients with advanced soft tissue sarcoma, according to topline results from a phase 3 clinical trial.

The open-label Study 309 enrolled 452 patients with locally advanced or metastatic adipocytic sarcoma or leiomyosarcoma who had progressed on two prior therapies, including an anthracycline. The primary endpoint of the study was OS, with progression-free survival (PFS) as a secondary outcome measure.

Eisai, the company developing eribulin, announced plans to submit data from Study 309 to the Food and Drug Administration (FDA) during 2015 for regulatory approval. Data from the randomized phase 3 trial will be presented at an upcoming medical meeting.

"The study results show the potential role of eribulin for the treatment of patients with soft tissue sarcoma, where a need exists for additional treatment options," Kenichi Nomoto, president of the Oncology Product Creation Unit at Eisai Inc, the developer of eribulin, said in a statement. "We are excited about the results of this study, which reinforces our continued commitment to discovering potential new treatment options for people with rare and orphan cancers."

In May 2012, the FDA granted eribulin an orphan designation as a treatment for patients with advanced soft tissue sarcoma. This designation was based primarily on results from a phase 2 study, which demonstrated that treatment with eribulin delayed progression for patients with advanced soft tissue sarcoma.

At 12 weeks, the PFS rate was 31.6 percent for patients with leiomyosarcoma, 46.9 percent in those with adipocytic sarcoma, 21.1 percent in synovial sarcomas and 19.2 percent in other types of sarcoma. Specifically in patients with leiomyosarcoma, the median PFS was three months and the median OS was 20 months. The PFS for patients with adipocytic sarcoma was three months and the median OS was 10 months.

The most common moderate to severe adverse events were neutropenia, leucopenia, anemia and fatigue. The most common side effects in the phase 3 study were neutropenia, fatigue, nausea, alopecia and constipation.

In studies looking at single-agent dacarbazine in previously treated advanced soft tissue sarcoma, the PFS rate at 12 weeks was around 35 percent with an approximate overall survival of eight months.

Eribulin is a synthetic analog of a polyether macrolide derived from the marine sponge Halichondria okadai. The agent inhibits the assembly of microtubules by binding to the tubulin vinca domain, causing cell cycle arrest.

The FDA initially approved eribulin as Halaven in 2010 for the treatment of patients with metastatic breast cancer following at least two chemotherapeutic regimens, including an anthracycline and a taxane in the adjuvant or metastatic setting. 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 3 EMBRACE trial.