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Ixabepilone in Combination with Capecitabine and as Monotherapy for Treatment of Advanced Breast Cancer Refractory to Previous Chemotherapies

Authors' Affiliations: ¹ Office of Oncology Drug Products, ² Office of Biostatistics, ³ Office of Clinical Pharmacology, and ⁴ Office of New Drug Quality Assurance, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland

Requests for reprints: Edvardas Kaminskas, Division of Drug Oncology Products, Food and Drug Administration, Building 22, Room 2181, 10903 New Hampshire Avenue, Silver Spring, MD 20903. Phone: 301-796-1383; Fax: 301-796-9845; E-mail: edvardas.kaminskas{at}fda.hhs.gov.

Abstract

Purpose: To 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 Design: Data 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.

Results: In 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.

Conclusions: On 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.