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

• Published in: Clinical cancer research Vol. 14; no. 14; pp. 4378 - 4384
• Main Authors: Lechleider, Robert J, Kaminskas, Edvardas, Jiang, Xiaoping, Aziz, Robeena, Bullock, Julie, Kasliwal, Ravindra, Harapanhalli, Ravi, Pope, Sarah, Sridhara, Rajeshwari, Leighton, John, Booth, Brian, Dagher, Ramzi, Justice, Robert, Pazdur, Richard
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 15-07-2008
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Capecitabine; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Disease-Free Survival; Drug Resistance, Neoplasm; Epothilones - administration & dosage; Epothilones - adverse effects; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - analogs & derivatives; Humans; Ixempra; Middle Aged; Neoplasm Metastasis - drug therapy; Neoplasm Recurrence, Local - drug therapy; new drug application; regulatory
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-0015

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.