Eribulin Shows Promise in Advanced Sarcoma

According to results from a randomized phase III study, eribulin (Halaven; Eisai) improves the overall survival (OS) of patients with advanced liposarcoma or leiomyosarcoma. The findings were presented by Patrick Schöffski, MD, MPH, head of medical oncology at University Hospitals Leuven in Belgium, at the American Society of Clinical Oncology's Annual Meeting in Chicago, IL, May 29–June 2.

Liposarcoma originates in fat tissue, and leiomyosarcoma in smooth muscle. Both are among the more common soft-tissue sarcomas, a highly heterogeneous group of rare cancers that is notoriously difficult to treat. “The efficacy of available drugs for initial therapy is very unsatisfactory, and patients with advanced metastatic disease have a very poor prognosis—their survival is typically 1 year or less,” Schöffski said.

Eribulin is a synthetic analog of the marine sponge product halichondrin B; it induces cytotoxicity by suppressing microtubule dynamics. Prior to this study, Schöffski carried out a phase II evaluation of eribulin's activity in four sarcoma subgroups. “The so-called ‘L sarcomas’ produced the strongest efficacy signal,” he said, “so it was a strategic decision to focus on them in a larger analysis.” Because of the overall rarity of these cancers, he added, “this clinical trial was a global effort involving more than 100 sarcoma centers in 22 countries.”

A total of 452 patients with advanced liposarcoma or leiomyosarcoma were enrolled in the study and randomly assigned to receive eribulin or the alkylating agent dacarbazine, a conventional chemotherapy. The median OS for patients treated with eribulin was 13.5 months, and 11.5 months for those given dacarbazine. Fatigue, nausea, and constipation were common adverse events in both treatment arms; patients on eribulin also experienced neutropenia and alopecia, while anemia and thrombocytopenia were observed among those on dacarbazine. These were “all typical side effects with both drugs,” Schöffski noted.

From Schöffski's perspective, even a 2-month increase in OS “is clinically meaningful, given the high unmet medical need of this rare, difficult-to-treat patient population.” This is also “the first phase III study in soft-tissue sarcoma to demonstrate improved survival with an investigational agent, compared to an active drug,” he added.

“I've been an oncologist for over 20 years, and there's never been a sarcoma study showing a survival benefit with any new chemotherapy,” agreed Gary Schwartz, MD, associate director of the Herbert Irving Comprehensive Cancer Center at Columbia University in New York, NY. “It's a small step for cancer, but a giant one for sarcoma.”

Schwartz was initially skeptical that eribulin would be any more effective in these soft-tissue sarcomas than conventional agents like dacarbazine or doxorubicin. Preclinical models suggest that besides antimitotic activity, eribulin may remodel tumor vasculature and reverse epithelial–mesenchymal transition; these effects could contribute to the drug's increased efficacy, Schöffski noted. However, Schwartz cautioned that “the science has yet to be fully explored and understood.”

Eribulin is approved in 59 countries as monotherapy for patients with advanced breast cancer. Schöffski said he strongly believes “it should also be indicated for these two sarcoma subtypes, given how few treatment options exist.”