A phase III multicenter study of eribulin mesylate in women with previously treated metastatic breast cancer failed to meet its co-primary endpoints of improved progression-free survival (PFS) and overall survival (OS) compared with capecitabine. Nevertheless, this was the first study demonstrating eribulin to be active in the first-, second- and third-line setting in metastatic breast cancer. Although no statistically significant superiority over capecitabine was shown, the OS with eribulin was numerically better than with capecitabine. Moreover, exploratory analyses suggest possible benefits of eribulin in specific subsets of patients.
Eribulin is a non-taxane microtubule dynamics inhibitor. In a previous Phase III trial, eribulin demonstrated a statistically significant improvement in OS vs. current treatments and a manageable toxicity profile in heavily pre-treated patients with metastatic breast cancer. Following these data, the FDA approved eribulin for the treatment of patients with metastatic breast cancer who previously received an anthracycline and a taxane and at least two cytotoxic chemotherapy treatment regimens for metastatic breast cancer. In the study at hand, Kaufman and colleagues examined whether eribulin would be effective as an earlier-line treatment in women with metastatic breast cancer.
To this end, a total of 1,102 patients were randomly assigned to eribulin or capecitabine. Patients in the study all received prior anthracycline- and taxane-based therapy and received the study drug as the first, second or third line of therapy for metastatic disease. The co-primary endpoints were OS and PFS, while secondary endpoints included objective response rate (ORR), quality of life (QoL), duration of response, 1-, 2- and 3-year survival, and safety. The median OS for patients assigned to eribulin was 15.9 months compared with 14.5 months for patients assigned to capecitabine (HR[95%CI]: 0.879[0.77-1.003]; p= 0.056). Median PFS was 4.1 months for eribulin treated patients compared to 4.2 months for capecitabine (HR[95%CI]: 1.079[0.932-1.250]; p= 0.305). Exploratory analyses of patient subsets showed that the median OS in women with HER2-negative breast cancer was 15.9 months with eribulin compared with 13.5 months with capecitabine (HR[95%CI]: 0.838[0.715-0.983]; p= 0.030). In women with triple-negative breast cancer, which is a particularly aggressive subset, the median OS was 14.4 months with eribulin compared with 9.4 months with capecitabine (HR[95%CI]: 0.702[0.545-0.906]).
The most common adverse events for eribulin and capecitabine (>20% all grades) were neutropenia (54.2% vs. 15.9%), hand-foot syndrome (0.2% vs. 45.1%) alopecia (34.6% vs. 4.0%), leukopenia (31.4% vs. 10.4%), diarrhea (14.3% vs. 28.8%) and nausea (22.2% vs. 24.4%).
In summary, although this study did not meet its primary endpoints, it is the first study demonstrating the activity of eribulin in earlier lines of treatment of metastatic breast cancer. As such, eribulin is an active therapy in this setting, and overall it has potentially comparable activity to capecitabine, which is a widely used treatment in this patient population. Interestingly, exploratory analyses suggest possible benefits of eribulin in specific subsets of patients, which is sufficient to warrant further study.
P. Kaufman, A. Awada, C. Twelves et al. A Phase III, open-label, randomized, multicenter study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Presented at SABCS 2012; Abstract S6-6.