Treating advanced sarcoma with the chemotherapy agent eribulin improves overall survival compared with treatment with standard therapy with dacarbazine.
Treating advanced sarcoma with the chemotherapy agent eribulin improves overall survival compared with treatment with standard therapy with dacarbazine, according to the results of a randomized, open-label, multicenter phase III trial (abstract LBA10502) presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 to June 2, in Chicago.
“This is the first phase III trial investigating patients with soft-tissue sarcoma to demonstrate an overall survival benefit compared with an active agent,” said lead author Patrick SchÃ¶ffski, MD, MPH, head of the department of general medical oncology at University Hospitals Leuven in Leuven, Belgium.
Soft-tissue sarcoma is a heterogeneous family of rare diseases, and liposarcoma and leiomyosarcoma are among the more common subtypes. Patients with advanced, metastatic soft-tissue sarcoma have poor outcomes with limited treatment options.
Eribulin, a microtubule dynamics inhibitor, is a synthetic analog of halichondrin B, originating from a marine sponge product. It is primarily a cytotoxic compound that, based on preclinical findings, kills cancer cells via antimitotic effects, SchÃ¶ffski said.
In preclinical models, eribulin also affects tumor cells via vascular remodeling, reversal of epithelial-mesenchymal transition, suppression of migration, and invasion. The drug is approved in 59 countries as monotherapy in multiple lines for patients with advanced/metastatic breast cancer.
“The efficacy of available drugs for initial therapy of sarcomas is very unsatisfactory, and patients whose disease progresses despite two or more lines of treatment have a very poor prognosis,” SchÃ¶ffski said. Typically, survival is 1 year or less for the estimated 12,000 people who will be diagnosed this year in the United States with soft-tissue sarcoma.
In the study, 452 sarcoma patients, about three-quarters of them under age 65 years, were randomly assigned to receive either eribulin 1.4 mg/m2 intravenously on days 1 and 8 (228 patients) or dacarbazine 850–1,200 mg/m2 intravenously on day 1 (224 patients) every 21 days until disease progression. All patients had received at least two standard systemic treatment regimens, including an anthracycline.
The trial’s primary endpoint, overall survival, was met. “Patients treated with eribulin experienced a statistically significant improvement in median overall survival as compared with dacarbazine (13.5 months vs 11.5 months; hazard ratio = 0.768; P = .0169),” SchÃ¶ffski said. Median progression-free survival was 2.6 months in both arms.
Adverse events were in line with the known safety profiles, he said. The most common frequent treatment-related adverse events in the eribulin arm were neutropenia, fatigue, nausea, alopecia, and constipation; 8% of patients stopped treatment due to side effects.
Low platelet counts were more common in the dacarbazine group compared with the eribulin group. Grade 3 and 4 treatment-related side effects occurred more frequently with eribulin than dacarbazine.
“For a disease where such few treatment options exist, a 2-month improvement in survival is significant. The more treatments our patients have access to, the better their chances of improving life expectancy,” SchÃ¶ffski said.
Gary K. Schwartz, MD, professor of medicine at Columbia University Medical Center, commented: “This is a giant step forward in sarcoma. There has never been a positive study for survival in sarcoma.” The side effects are manageable, he added, and must be balanced against the drug’s benefits.