ANOTHER FAILURE OF IXABEPILONE

J Clin Oncol. 2010 Jun 7. [Epub ahead of print]
Randomized Phase III Trial of Ixabepilone Plus Capecitabine Versus Capecitabine in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane.
Sparano JA, Vrdoljak E, Rixe O, Xu B, Manikhas A, Medina C, Ventilari Da Costa SC, Ro J, Rubio G, Rondinon M, Perez Manga G, Peck R, Poulart V, Conte P.

Montefiore-Einstein Cancer Center, Bronx, NY; Center of Oncology, University Hospital Split, Split, Croatia; National Cancer Institute, Bethesda, MD; Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China; St Petersburg City Oncology Center, St Petersburg, Russia; Centro Medico San Roque, San Roque; Hospital Britanico and Hospital Frances, Buenos Aires, Ciudad De Buenos, Argentina; Interhospital III, Rio De Janeiro, Brazil; National Cancer Center, Seoul, Republic of Korea; University General Hospital Gregorio Maranon, Madrid, Spain; Bristol-Myers Squibb, Wallingford, CT; Bristol-Myers Squibb, Braine-l'Alleud, Belgium; and Department of Oncology and Hematology, University Hospital, Modena, Italy.
Abstract

PURPOSE We sought to determine whether the combination of ixabepilone plus capecitabine improved overall survival (OS) compared with capecitabine alone in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. PATIENTS AND METHODS A total of 1,221 patients with MBC previously treated with anthracycline and taxanes were randomly assigned to ixabepilone (40 mg/m(2) intravenously on day 1) plus capecitabine (2,000 mg/m(2) orally on days 1 through 14) or capecitabine alone (2,500 mg/m(2) on the same schedule) given every 21 days. The trial was powered to detect a 20% reduction in the hazard ratio (HR) for death. Results There was no significant difference in OS between the combination and capecitabine monotherapy arm, 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 impaired performance status (Karnofsky performance status 70% to 80%) in the combination arm (32% v 25%). In a secondary Cox regression analysis adjusted for performance status and other prognostic 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 improved progression-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. CONCLUSION This study confirmed a previous trial demonstrating improved PFS and response for the ixabepilone-capecitabine combination compared with capecitabine alone, although this did not result in improved survival.