ASCO 2015: Eribulin Extends Overall Survival for Heavily Pretreated Patients With Advanced Liposarcoma and Leiomyosarcoma
Heavily pretreated patients with intermediate- or high-grade liposarcoma or leiomyosarcoma had a 2-month increase in median overall survival when subsequently treated with eribulin (Halaven) rather than the standard drug dacarbazine. “For a disease where so few treatment options exist, a 2-month improvement in survival is significant,” noted Patrick Schöffski, MD, MPH, the lead author of the phase III study comparing the two agents. Dr. Schöffski, Head of the Department of General Medical Oncology, University Hospitals Leuven in Leuven, Belgium, presented the study results at the 2015 ASCO Annual Meeting in Chicago (Abstract LBA10502).
An estimated 12,000 people will be diagnosed with soft-tissue sarcoma in the United States this year. Patients with advanced, metastatic soft-tissue sarcoma have limited treatment options and poor outcomes, typically with survival of 1 year or less.
Eribulin belongs to a class of anticancer drugs known as microtubule dynamics inhibitors. “Eribulin is primarily a cytotoxic compound and has antimitotic effects in the preclinical models, but also in the clinic,” Dr. Schöffski explained at a press briefing. “In addition, preclinical work has shown that the drug also affects the tumor cells via other mechanisms, such as reversal of the epithelial-mesenchymal transition, suppression of tumor cell migration, and invasion.”
Eribulin is a synthetic analog of halichondrin B originating from a marine sponge product. The drug is approved for the treatment of advanced breast cancer in 59 countries, including the United States.
Met Primary Objective
The global study recruited patients at more than 100 sarcoma sites in 22 countries. The 452 study participants had received two or more lines of systemic therapy for advanced or metastatic disease. Patients with advanced leiomyosarcoma or adipocytic sarcoma (also called liposarcoma) were randomly assigned to treatment with eribulin or dacarbazine until disease progression. Eribulin at 1.4 mg/m2 was administered intravenously to 228 patients on days 1 and 8 every 21 days. Dacarbazine was administered intravenously to 224 patients on day 1 every 21 days, at a dose of 850, 1,000 or 1,200 mg/m2, with the dose selected by the investigators.
“The most important finding of this study was that the primary endpoint of overall survival was met. Eribulin had a favorable overall survival of 13.5 months, as compared to standard agent dacarbazine, which had an overall survival of 11.5 months. The hazard ratio was 0.768, and the P value was .0169,” Dr. Schöffski reported.
“This is the very first phase III trial investigating patients with soft-tissue sarcoma to demonstrate overall survival benefit of a new agent compared with an active agent,” Dr. Schöffski noted. “For me as a sarcoma oncologist, this is a clinically meaningful result, given the unmet medical need in this very rare and hard-to-treat family of diseases.”
“This is going to be very welcome news for patients with these two very rare sarcoma types, especially since we understand that patients in this study were very heavily pretreated, and active agents for this population are not readily available,” commented ASCO spokesperson and press briefing moderator Don S. Dizon, MD. Dr. Dizon is Clinical Co-Director of Gynecologic Oncology and Director of the Oncology Sexual Health Clinic at Massachusetts General Hospital, Boston.
Serious Side Effects More Frequent
No new safety findings were observed. Treatment-emergent adverse events occurred in almost all patients taking eribulin. The most frequent side effects were neutropenia, fatigue, nausea, alopecia, and constipation. Treatment-emergent adverse events led to drug discontinuation in 8% of patients in the eribulin group vs 5% in the dacarbazine group.
Grade ≥ 3 treatment-emergent adverse events occurred more frequently among patients receiving eribulin, 67.3% vs 56.3% for dacarbazine. Grade ≥ 3 neutropenia occurred in 35.4% of patients taking eribulin vs 15.6% taking dacarbazine. Thrombocytopenia was more common with dacarbazine, with grade ≥ 3 events occurring in 15.2% vs 0.4% with eribulin. Three deaths occurred among patients receiving dacarbazine, and ten deaths occurred among patients receiving eribulin, two attributed to therapy.
Several additional analyses are ongoing, including quality-of-life analysis, subgroup analysis, and biomarker tests. The results of those analyses will be reported at a later date.
This study received funding from Eisai Inc. Dr. Schöffski reported honoraria from Bayer, GlaxoSmithKline, Servier, Iteos Therapeutics, Mundipharma, Plexxikon, Swedish Orphan Biovitrum, Threshold Pharmaceuticals, ThromboGenics, Prime Oncology, Boehringer Ingelheim, Amgen Research Munich GmbH, Novartis Healthcare A/S, Pique, and Asia & Emerging Markets Innovative Medicine of AstraZeneca R&D; consulting or advisory roles with Bayer, GlaxoSmithKline, Servier, Iteos Therapeutics, Mundipharma, Plexxikon, Swedish Orphan Biovitrum, Threshold Pharmaceuticals, ThromboGenics, Boehringer Ingelheim, Amgen Research Munich GmbH, Novartis Healthcare A/S, Pique, and Asia & Emerging Markets Innovative Medicine of AstraZeneca R&D; speakers bureau with GlaxoSmithKline, Prime Oncology, Swedish Orphan Biovitrum, and Novartis Healthcare A/S. For full disclosures of the study authors, view the study abstract at abstract.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
