To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Investigational Agent Ixabepilone Improves Response Rates When Added to Capecitabine Therapy: Presented at ASCO-Breast URL: http://www.pslgroup.com/dg/22B6D2.htm Doctor's Guide September 8, 2008
By Lisa M. Cockrell, PhD WASHINGTON, DC -- September 8, 2008 -- The addition of the novel epothilone analogue ixabepilone to the antineoplastic agent capecitabine results in superior rates of progression-free survival (PFS) and response compared with capecitabine alone, according to results of 2 large, phase 3 trials with more than 2,000 patients. Gabriel Hortobagyi, MD, Multidisciplinary Breast Cancer Research Program and Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, and colleagues presented the findings here on September 5 at the American Society of Clinical Oncology's Annual Breast Cancer Symposium (ASCO-Breast). The researchers reviewed the efficacy and safety results of 2 randomised, phase 3 trials that evaluated the combination of ixabepilone and capecitabine in the setting of metastatic or locally-advanced breast cancer. The pivotal CA163-046 trial randomised 752 patients who were determined to have resistance to previous anthracycline and taxane therapy using strict resistance criteria. The confirmatory CA163-048 trial randomised 1,221 patients who were either pretreated with or resistant to an anthracycline and a taxane. Baseline characteristics were essentially comparable between these trials, except that half of patients enrolled in CA163-046 were resistant to prior therapy, while nearly all patients in CA163-048 were resistant. Both trials were identically designed and randomised patients to treatment with ixabepilone plus capecitabine or capecitabine monotherapy. The primary study endpoints were PFS in the CA163-046 trial and overall survival (OS) in the CA163-048 trial. Secondary endpoints included overall response (OR) rate, and safety. In both studies, the ixabepilone/capecitabine combination produced a prolonged median PFS compared with capecitabine monotherapy. Median PFS in CA163-046 was 5.3 and 3.8 months, respectively (P = .0011), and in CA163-048 it was 6.2 and 4.4 months (P = .0005). According to the investigators, a further analysis of PFS in prespecified subsets of patients from the confirmatory CA163-048 trial found a clinically meaningful increase in PFS with ixabepilone in patients with triple-negative disease (oestrogen receptor-negative; progesterone receptor-negative, human epidermal growth factor receptor 2). Median PFS within this subgroup was 4.2 in the combination arm and 1.8 months in the monotherapy arm (hazard ratio: 0.64). Superior OR rates were achieved by the combination group compared with the monotherapy arm. In the CA163-046 trial, the OR rate was 42.1% versus 22.5%, respectively, while in the CA163-048 trial the OR rate was 43.3% versus 28.8%, respectively. Although a trend towards a superior OS was noted in the combination arms of both trials, neither reached statistical significance. Interestingly, a statistical improvement in OS was noted in symptomatic patients, identified as having a Karnofsky performance status of 70 to 80. Median OS for the ixabepilone plus capecitabine arm versus capecitabine alone in the CA163-046 study was 10.1 versus 7.8 months, respectively (P = .0328) and in the CA163-048 study it was 14.0 versus 11.3 months, respectively (P = .0189). Addition of ixabepilone resulted in an increased incidence of haematological toxicities, including neutropenia, leukopenia, thrombocytopenia, and anaemia. Patients in the ixabepilone arm also had an increased incidence of some nonhaematological toxicities, such as peripheral neuropathy, fatigue, myalgia, arthralgia, and toxic death. The investigators concluded that addition of ixabepilone to capecitabine resulted in clinically meaningful efficacy, shown by superior improvements in both PFS and OR rate. Because this combination was shown to be active in a large, heavily pretreated patient population, future trials are planned to evaluate ixabepilone versus taxanes as first-line therapy and adjuvant therapy in breast cancer. Funding for the studies was provided by Bristol-Myers Squibb. [Presentation title: Novel Synthetic Epothilone Agent Ixabepilone Significantly Superior in Two Phase III Clinical Trials. Abstract 186] --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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