Christopher Twelves, MD
Treatment with eribulin mesylate (Halaven) improved overall survival (OS) of patients with triple-negative and HER2-negative metastatic breast cancer compared with standard chemotherapies, according to a presentation at the 2014 National Cancer Research Institute Conference in Liverpool.
The extension in survival was found in data from patients with locally recurrent metastatic breast cancer following progression on a taxane and anthracycline treated with eribulin across 2 large open-label phase III trials. In the EMBRACE trial, third-line treatment with eribulin was compared with treatment of physicians’ choice. In Study 301, eribulin was compared with capecitabine in patients who had received 0-2 prior therapies.
“Our results show a substantial improvement in survival for women with metastatic triple-negative breast cancer, and a more modest, but significant, benefit for those with HER2-negative breast cancers," lead investigator Christopher Twelves, MD, professor of Clinical Cancer Pharmacology and Oncology at the Leeds Institute of Cancer and Pathology and St James's Institute of Oncology, Leeds, UK, said in a statement. “Eribulin has previously been offered to women who’ve already been through several lines of chemotherapy."
In both trials, intravenous eribulin was administered at 1.4 mg/m2
on days 1 and 8 every 21 days. OS was analyzed by 2-sided stratified log-rank tests and Cox regression in subgroups of patients with HER2-negative, HER2-positive, and triple-negative breast cancer (TNBC). The two studies enrolled 1864 patients — 31.5% of patients were treated in the second-line setting and 32.7% in the third-line.
In the intent-to-treat analysis, median OS was 15.2 months with eribulin versus 12.8 months in the control arm (HR = 0.85; 95% CI, 0.77-0.95, P
= .003). In patients with HER2-negative disease, the median with eribulin was 15.2 versus 12.3 months (HR= 0.82; 95% CI, 0.72-0.93, P
= .002). For patients with TNBC, the median OS was 12.9 months with eribulin compared with 8.2 months in the control (HR = 0.74; 95% CI, 0.60-0.92, P
A statistically significant benefit was not seen in patients with HER2-positive disease. For this population, the median OS with eribulin was 13.5 versus 12.2 months (HR = 0.82; 95% CI, 0.62-1.06, P
Researchers did not uncover any unexpected side effects in the combined analysis with eribulin. In Study 301, the most common adverse events for eribulin and capecitabine were neutropenia (54% vs 16%), hand-foot syndrome (<1% vs 45%), alopecia (35% vs 4%), leukopenia (31% vs 10%), diarrhea (14% vs 29%), and nausea (22% vs 24%).
When data from Study 301 were initially presented at the 2012 San Antonio Breast Cancer Symposium, researchers noted that patients with TNBC seemed to experience an extension in OS of approximately 5 months over capecitabine. A prespecified exploratory subgroup analysis from this study showed that patients with TNBC, ER-negative, or HER2-negative experienced a greater benefit in OS with eribulin compared with capecitabine.
In data presented at the 2013 ASCO Annual Meeting, other populations of patients from Study 301 were identified who benefited more from eribulin than capecitabine. For OS, patients with non-visceral disease (HR = 0.51; 95% CI, 0.33-0.80), with >2 organs involved (HR = 0.75; 95% CI, 0.62-0.90), who had progressed >6 months after last chemotherapy (HR = 0.70; 95% CI 0.52-0.95), or who had received an anthracycline and/or a taxane in the metastatic setting (HR = 0.84; 95% CI, 0.72-0.98).
Eribulin is a synthetic analogue of halichondrin B, a product that is isolated from the marine sponge Halichondria okadai
. Eribulin is designed to inhibit microtubule polymerization without affecting depolymerization. This results in apoptosis through an irreversible mitotic block at the G2-M phases.
In November 2010, the FDA approved eribulin as a treatment for patients with metastatic breast cancer following the administration of at least 2 regimens with an anthracycline and a taxane. This approval was based on data from the EMBRACE trial, which demonstrated a statistically significant improvement in OS for patients receiving eribulin compared with physician's choice of therapy.