Metastatic Breast Cancer Treatment Challenges - Episode 9
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Cytotoxics remain an important class of drugs in the treatment of patients with metastatic breast cancer (MBC), despite a growing focus on targeted therapies, notes moderator Adam M. Brufsky, MD, PhD. One such agent, eribulin mesylate, has been the focus of several recent clinical trials. This agent was approved in the United States in 2010 for the treatment of MBC following the administration of at least two regimens that include an anthracycline and a taxane.
This approval was based on the open-label, randomized, phase III EMBRACE trial that compared eribulin to physician's choice in heavily pretreated patients with MBC, explains Sara Hurvitz, MD. In this situation, physician's choice included several treatments, including hormonal therapy, palliative care, and chemotherapy. The trial found that overall survival (OS) was significantly prolonged by single-agent eribulin.
In another study, referred to as Study 301, eribulin was compared to capecitabine as a second-line treatment for patients with HER2-negative MBC. This trial did not find a significant advantage for eribulin over capecitabine, in terms of PFS or OS, explains Hurvitz. However, a subset analysis indicated a trend toward benefit with eribulin in patients with triple-negative breast cancer, which is currently an area of unmet need.
In the preclinical setting eribulin demonstrated a novel antimesenchymal mechanism of action, suggests Joyce A. O'Shaughnessy, MD. This unique property could be responsible for the lack of progression-free survival benefit with eribulin in both Study 301 and the EMBRACE trial. Furthermore, O'Shaughnessy believes, eribulin could work to reverse the epithelial-mesenchymal transition, rendering other chemotherapeutics more effective. As a result, the agent seems most effective in patients that demonstrate a predominant mesenchymal biology, suggests Hope S. Rugo, MD.
To further explore this theory, a neoadjuvant trial will examine gene expression profiling from serial breast cancer biopsies to explore the antimesenchymal effects of eribulin, notes Edith A. Perez, MD. Additionally, a subanalysis from Study 301 will apply an alternate RECIST definition of progression to the findings. This analysis will likely be presented at the ESMO Annual Meeting in September, Perez hopes.