• Robert J Lechleider, Edvardas Kaminskas, Xiaoping Jiang, Robeena Aziz, Julie Bullock, Ravindra Kasliwal, Ravi Harapanhalli, Sarah Pope, Rajeshwari Sridhara, John Leighton, Brian Booth, Ramzi Dagher, Robert Justice, and Richard Pazdur.
• Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20903, USA.
• Clin Cancer Res. 2008 Jul 15; 14 (14): 4378-84.

PurposeTo describe the considerations leading to marketing approval of ixabepilone in combination with capecitabine and as monotherapy for the treatment of advanced breast cancer that is refractory to other chemotherapies.Experimental DesignData from one randomized multicenter trial comparing combination therapy with ixabepilone and capecitabine to capecitabine alone were analyzed for support of the combination therapy indication. For monotherapy, a single-arm trial of ixabepilone was analyzed. Supporting data came from an additional single-arm combination therapy study and two single-arm monotherapy studies.ResultsIn patients with metastatic or locally advanced breast cancer who had disease progression on or following an anthracycline and a taxane, ixabepilone plus capecitabine showed an improvement in progression-free survival compared with capecitabine alone {median progression-free survival, 5.7 [95% confidence interval (95% CI), 4.8-6.7] versus 4.1 (95% CI, 3.1-4.3) months, stratified log-rank P < 0.0001; hazard ratio, 0.69 (95% CI, 0.58-0.83)}. As monotherapy for patients who had disease progression on or following an anthracycline, a taxane, and capecitabine, ixabepilone as monotherapy showed a 12% objective response rate by independent blinded review and 18% by investigator assessment. The major toxicities from ixabepilone therapy were peripheral neuropathy and myelosuppression, particularly neutropenia.ConclusionsOn October 16, 2007, the Food and Drug Administration approved ixabepilone for injection in combination with capecitabine or as monotherapy for the treatment of patients with advanced breast cancer who have experienced disease progression on previous chemotherapies.

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