Limited proven treatment options exist for patients with metastatic breast cancer (MBC) resistant to anthracycline and taxane treatment. Ixabepilone, a novel semisynthetic analog of epothilone B, has demonstrated single-agent activity in MBC resistant to anthracyclines and taxanes. In combination with capecitabine in a phase III trial (CA163-046) in this setting, ixabepilone prolonged progression-free survival and increased objective response rate relative to capecitabine (Thomas et al. J Clin Oncol 25:5210-5217, 2007). Here, we report the results of overall survival (OS), a secondary efficacy endpoint from the CA163-046 trial. Seven hundred fifty-two patients with MBC resistant to anthracyclines and taxanes were randomized to ixabepilone (40 mg/m2 intravenously on day 1 of a 21-day cycle) plus capecitabine (2,000 mg/m 2 orally on days 1 through 14 of a 21-day cycle) or capecitabine alone (2,500 mg/m2 on the same schedule). Patients receiving ixabepilone plus capecitabine treatment had a median survival of 12.9 months compared to 11.1 months for patients receiving capecitabine alone (HR = 0.9; 95%CI: 077-1.05; P = 0.19). This observed increase in median OS favored the combination; however, the difference was not statistically significant. Predefined subset analyses showed a clinically meaningful increase in OS in KPS 70-80 patients receiving ixabepilone plus capecitabine (HR = 0.75; 95% CI: 0.58-0.98). Ixabepilone plus capecitabine did not show a significant improvement in survival compared to capecitabine alone in patients with MBC resistant to anthracyclines and taxanes. The observed differences in survival favored the combination arm. A clinical benefit was also seen in patients in the KPS 70-80 subgroup (ClinicalTrials.gov number, NCT000080301).
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Conflict of interest statement GH has served as a consultant for Bristol-Myers Squibb and Novartis and has a commercial research grant from Novartis; LF has served as a consultant for Bristol-Myers Squibb; VC has received honoraria from Eli Lilly and Novartis and has served as a consultant for Astra Zeneca; JJ has served as a consultant for Bristol-Myers Squibb and Glaxo SmithKleine; XP has received honoraria from Roche, Glaxo SmithKleine, and Novartis, has served as a consultant for Roche and has received commercial research support from Roche; LV has received honoraria from Bristol-Myers Squibb, commercial research grant from Bristol-Myers Squibb, Curagen, Imclone, and Glaxo SmithKleine, and has served as a consultant for Bristol-Myers Squibb, Bayer, and Onyx; HG, RKL, HCC GL, FM BX, and HR have no financial relationships to disclose; RP and PM are employees of Bristol-Myers Squibb.
All Science Journal Classification (ASJC) codes
- Cancer Research