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Eribulin improves survival for patients with advanced sarcomas, but questions remain
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Eribulin mesylate significantly improved survival compared with dacarbazine among patients with advanced intermediate or high-grade liposarcoma or leiomyosarcoma who failed first- and second-line treatments, according to randomized, phase 3 study results published in The Lancet.
The results — originally presented at the 2015 ASCO Annual Meeting — showed a 2-month improvement in survival with the chemotherapy drug eribulin mesylate (Halaven, Eisai; 13.5 months vs. 11.5 months), representing the first time an agent significantly improved OS in patients with aggressive liposarcoma or leiomyosarcoma on a clinical trial.
“Soft-tissue sarcomas are relatively rare and can be very difficult to treat,” Patrick Schöffski, MD, MPH, head of the department of general medical oncology and the laboratory of experimental oncology at University Hospitals Leuven, Belgium, said at the time of the ASCO presentation. “The efficacy of available drugs for initial therapy is very unsatisfactory, and patients whose disease progresses despite two or more lines of treatment have a very poor prognosis.
“For a disease where such few treatment options exist, a 2-month improvement in survival is significant,” he added. “The more treatments our patients have access to, the better their chances of improving life expectancy.”
The analysis included data from 452 patients (67% women; 79% aged younger than 65 years), 228 of whom were randomly assigned to 1.4 mg/m² IV eribulin on days 1 and 8 every 21 days. The other 224 patients received between 850 mg/m² and 1,200 mg/m² IV dacarbazine on day 1 every 21 days. All patients were treated until disease progression.
OS served as the study’s primary endpoint. Secondary endpoints including PFS, PFS rate at 12 weeks and safety.
The median OS was 13.5 months in the eribulin mesylate arm and 11.5 months in the dacarbazine arm (HR = 0.77; 95% CI, 0.62-0.95).
Median PFS was 2.6 months in both arms (HR = 0.88; 95% CI, 0.71-1.09). The rate of 12-week PFS was 33% in the eribulin mesylate arm and 29% in the dacarbazine arm.
More patients assigned eribulin mesylate required dose reductions (26% vs. 14%) and discontinued treatment due to adverse events (8% vs. 5%).
Despite the improvement in survival, the use of eribulin mesylate for soft-tissue sarcomas remains uncertain, Robin J. Young, MBChB, MRCP, MSc, PhD, and Penella J. Woll, BMedSci, MB BS, PhD, FRCP, both of Weston Park Hospital at University of Sheffield in the U.K., wrote in an accompanying editorial.
The study was not designed or powered for drawing conclusions, they wrote.
For example, the prespecified HR for survival was 0.71, which was not reached in the analysis, despite an improvement in survival that was greater than expected. There also were no changes in PFS, a trend also observed in studies of eribulin mesylate for the treatment of advanced breast cancer.
Additionally, they noted that the researchers could have chosen a number of drugs with activity in treatment-refractory disease as the control. The chosen control, dacarbazine, has modest efficacy, they wrote.
Thirty-four percent of patients assigned eribulin mesylate received dacarbazine after the study, which could have reduced the OS differences.
Thus, Young and Woll questioned whether eribulin mesylate could be used earlier in the treatment pathway.
“Given the low number of objective responses, eribulin is not attractive as a first-line option for advanced soft tissue sarcoma,” Young and Woll wrote. “If eribulin enhances the response to subsequent chemotherapy, should eribulin be used in combination or sequenced with other systemic treatments, and with which other drugs?
“Further study of mode of action of eribulin and identification of biomarkers to guide patient selection would help to place it in the algorithm of treatments for relapse,” they wrote – by Anthony SanFilippo
Disclosures: This study was funded by Eisai. Schöffski reports honoraria from and speakers bureau or consulting/advisory roles with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Iteos Therapeutics, Mundipharma, Novartis, Pique, Plexxikon, Prime Oncology, SERVIER, Swedish Orphan Biovitrum, Threshold Pharmaceuticals and ThromboGenics. Young and Woll report no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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