Abstract
Successful management of breast cancer in the metastatic setting is often confounded by resistance to chemotherapeutics, in particular anthracyclines and taxanes. The limited number of effective treatment options for patients with more aggressive biological subtypes, such as triple-negative metastatic breast cancer, is especially concerning. As such, a therapy clinically proven to be effective in this subtype would be of great value. Ixabepilone, a novel synthetic lactam analog of epothilone B, demonstrated better clinical outcomes in metastatic disease, particularly in triple-negative breast cancer. Most recently, studies have shown the activity of ixabepilone in the neoadjuvant setting, suggesting a role for this drug in primary disease. Notably, treating in the neoadjuvant setting might allow clinicians to explore the predictive value of biomarkers and response to treatment, as pharmacogenomic approaches to therapy continue to evolve. In this article, we review the efficacy and safety data of ixabepilone as a monotherapy and as a component of combination therapy for metastatic and primary breast cancer.
Highlights
Breast cancer is the most prevalent malignancy in women and in its metastatic state, the second most common cause of mortality [1]
Results from clinical trials of patients treated with ixabepilone 40 mg/m2 demonstrated that the exposure was comparable to that of mice treated with ixabepilone 10 mg/m2, and that 40 mg/m2 offered clinically significant antitumor activity [33]
The single-arm phase 2 trial 081 assessed the efficacy of ixabepilone (40 mg/m2 intravenous [IV] over 3 hours every 3 weeks) in women with metastatic breast cancer (MBC) who were heavily pretreated with an anthracycline, a taxane, and capecitabine
Summary
Breast cancer is the most prevalent malignancy in women and in its metastatic state, the second most common cause of mortality [1]. In 2011, an estimated 230,480 of women were diagnosed with new cases of invasive breast cancer in the United States and 39,520 died from the disease [2]. Despite advances in treatment strategies, metastatic breast cancer (MBC) remains incurable and the goals of therapy range from symptom palliation to extending survival. Breast cancer treatments can be categorized as: (a) estrogen receptor (ER)-positive and treatable by endocrine therapy; (b) HER2 overexpressed/amplified, treatable with trastuzumab or other HER2-targeted therapies; or (c) triple-negative (TN), with no current specific therapeutic biomarker, typically treated with cytotoxic chemotherapy. This review will outline the treatment strategies in the management of MBC and focus on the role of novel cytotoxic agents, ixabepilone, in this disease
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