randomised phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane

PurposeWe sought to determine whether the combination of ixabepilone plus capecitabine improvedoverall survival (OS) compared with capecitabine alone in patients with metastatic breast cancer(MBC) previously treated with anthracyclines and taxanes.Patients and MethodsA total of 1,221 patients with MBC previously treated with anthracycline and taxanes wererandomly assigned to ixabepilone (40 mg/m2 intravenously on day 1) plus capecitabine (2,000mg/m2 orally on days 1 through 14) or capecitabine alone (2,500 mg/m2 on the same schedule)given every 21 days. The trial was powered to detect a 20% reduction in the hazard ratio (HR)for death.ResultsThere was no significant difference in OS between the combination and capecitabine monotherapyarm, the primary end point (median, 16.4 v 15.6 months; HR 0.9; 95% CI, 078 to 1.03;P .1162). The arms were well balanced with the exception of a higher prevalence of impairedperformance status (Karnofsky performance status 70% to 80%) in the combination arm (32% v25%). In a secondary Cox regression analysis adjusted for performance status and otherprognostic factors, OS was improved for the combination (HR 0.85; 95% CI, 0.75 to 0.98;P .0231). In 79% of patients with measurable disease, the combination significantly improvedprogression-free survival (PFS; median, 6.2 v 4.2 months; HR 0.79; P .0005) and response rate(43% v 29%; P .0001). Grade 3 to 4 neuropathy occurred in 24% treated with the combination,but was reversible.ConclusionThis study confirmed a previous trial demonstrating improved PFS and response for theixabepilone-capecitabine combination compared with capecitabine alone, although this did not result inimproved survival.