Kenichi Nomoto, PhD
Treatment with eribulin mesylate (Halaven) significantly extended overall survival (OS) compared with dacarbazine in patients with advanced soft tissue sarcoma, according to topline results from a phase III clinical trial.
The open-label study, titled 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 FDA during 2015 for regulatory approval. Data from the randomized phase III 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, PhD, president of the Oncology Product Creation Unit at Eisai, 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 II study, which demonstrated that treatment with eribulin delayed progression for patients with advanced soft tissue sarcoma.
In the phase II study, 128 patients with adipocytic, leiomyosarcoma, synovial, or other subtypes of sarcoma received eribulin at 1.4 mg/m2
on day 1 and 8 of each 21-day cycle, which was the same dose used in the phase III study. Those enrolled had received no more than two prior lines of chemotherapy.
At 12 weeks, the PFS rate was 31.6% for patients with leiomyosarcoma, 46.9% in those with adipocytic sarcoma, 21.1% in synovial sarcomas, and 19.2% in other types of sarcoma. Specifically in patients with leiomyosarcoma, the median PFS was 3 months and the median OS was 20 months. The PFS for patients with adipocytic sarcoma was 3 months and the median OS was 10 months.
The most common grade 3/4 adverse events were neutropenia (52%), leucopenia (35%), anemia (7%), fatigue (7%), and febrile neutropenia (6%). The most common adverse events in the phase III study were neutropenia, fatigue, nausea, alopecia and constipation, Eisai noted.
In studies looking at single-agent dacarbazine in previously treated advanced soft tissue sarcoma, the PFS rate at 12 weeks was around 35% with an approximate overall survival of 8 months.
Eribulin is a synthetic analog of halichondrin B, 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 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 III EMBRACE trial.
"Overall Survival is recognized as the most definitive cancer outcome and is universally accepted as the direct measure of benefit in cancer treatments, Gary Hendler, chief executive officer at Eisai EMEA and the president of the Global Oncology Business Unit, said in a statement. “This study demonstrates that eribulin has the potential to become an important additional treatment option for patients with this aggressive and rare cancer that requires chemotherapy."