Ixabepilone and eribulin mesylate: two novel agents approved for the chemotherapeutic treatment ofmetastatic breast cancer

Author(s): Yael S Zack, Linda T Vahdat

While the majority of breast cancer patients present with early stage disease, 40% of these patients will eventually progress to metastatic disease. Resistance to existing chemotherapeutic agents continues to pose a challenge in the management of these patients. This review will analyze the two most recently approved chemotherapy drugs for the treatment of breast cancer; ixabepilone and eribulin mesylate. Ixabepilone is a semisynthetic analog of epothilone B, and is thought to overcome taxane resistance via disruption to microtubule homeostasis. Two Phase III studies, one by Rugo et al. and the other by Thomas et al., showed improvement in progression-free survival with the combination of ixabepilone and capecitabine to approximately 6 months compared with 4.2 months in the capecitabine-alone group in both trials. These resulted in ixabepilone being approved for use alone or in combination with capecitabine for the treatment of locally advanced or metastatic breast cancer after failure of an anthracycline and a taxane in either the adjuvant or the metastatic setting. The drug has been shown to have activity even in heavily pretreated patients who have received at least two prior chemotherapy regimens for the treatments of metastatic disease. The main adverse events were noted to be fatigue, cytopenias and peripheral sensory neuropathy, all of which were manageable and reversible. Eribulin mesylate is another novel agent that has been approved for the treatment of metastatic breast cancer. It functions by inhibiting mitotic-spindle formation and has demonstrated efficacy against various taxane-resistant tumor cell lines. Median progression-free survival was approximately 3 months and overall survival ranged from 9 to 13 months amongst the various trials. Eribulin mesylate is approved to treat patients with metastatic breast cancer who have received at least two prior chemotherapy regimens for metastatic disease, including both anthracycline- and taxane-based chemotherapy regimens. The most common toxicities observed were fatigue, nausea, cytopenias and peripheral neuropathy. In conclusion, both drugs provide additional options for patients who have progressed on other agents.