Ixabepilone: clinical role in metastatic breast cancer

Abstract

Ixabepilone has shown promising clinical data in metastatic breast cancer (MBC) and may be particularly valuable in patients showing progression after treatment with standard chemotherapy. This article reviews the developing clinical profile of ixabepilone in MBC. Unlike taxanes and anthracyclines, ixabepilone has low susceptibility to multiple mechanisms of tumor cell resistance and has activity against tumors resistant to taxanes and/or anthracyclines. In phase II studies, single-agent ixabepilone resulted in objective response rates ranging from 11.5% to 57% in patients who had locally advanced or metastatic breast cancer, including patients who were treated as first-line therapy or in resistant patients who had received multiple lines of previous treatment. In two large phase III studies in women who had locally advanced or MBC pretreated with or resistant to taxanes and/or anthracyclines, a combination of ixabepilone plus capecitabine was superior to capecitabine alone in terms of progression-free survival and response rates. The efficacy of ixabepilone has also been shown in subsets, including patients with poor prognosis, the first-line metastatic setting, and in triple-negative disease. Studies are underway to investigate this agent in combination with biologics. A recent three-arm study has shown the activity and tolerability of ixabepilone plus bevacizumab; however, comparative data are not yet available. The toxicity profile of ixabepilone is generally manageable and predictable. The most common adverse events associated with ixabepilone include peripheral neuropathy and neutropenia. Ixabepilone appears to offer a promising alternative chemotherapeutic agent for patients with MBC who progress on various taxanes, anthracyclines, and capecitabine.