Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment

Abstract

PurposeEffective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed to compare ixabepilone plus capecitabine versus capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer.Patients and MethodsSeven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m2intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m2orally on days 1 through 14 of a 21-day cycle, or capecitabine alone 2,500 mg/m2on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review.ResultsIxabepilone plus capecitabine prolonged progression-free survival relative to capecitabine (median, 5.8 v 4.2 months), with a 25% reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P = .0003). Objective response rate was also increased (35% v 14%; P < .0001). Grade 3/4 treatment-related sensory neuropathy (21% v 0%), fatigue (9% v 3%), and neutropenia (68% v 11%) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3% v 1%, with patients with liver dysfunction [≥ grade 2 liver function tests] at greater risk). Capecitabine-related toxicities were similar for both treatment groups.ConclusionIxabepilone plus capecitabine demonstrates superior efficacy to capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.