Journal of Clinical Oncology, Vol 23, No 4 (February 1), 2005: pp. 792-799
© 2005 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2005.05.098
Randomized Phase III Trial of Capecitabine Compared With Bevacizumab Plus Capecitabine in Patients With Previously Treated Metastatic Breast Cancer
Kathy D. Miller,
Linnea I. Chap,
Frankie A. Holmes,
Melody A. Cobleigh,
P. Kelly Marcom,
Louis Fehrenbacher,
Maura Dickler,
Beth A. Overmoyer,
James D. Reimann,
Amy P. Sing,
Virginia Langmuir,
Hope S. Rugo
From the Indiana University, Indianapolis, IN; University of California Los Angeles, Los Angeles; Kaiser Northern California, Vallejo; Genentech Inc, South San Francisco; University of California San Francisco, San Francisco, CA; US Oncology, Houston, TX; Rush-Presbyterian-St Luke's Medical Center, Chicago, IL; Duke University, Durham, NC; Memorial Sloan Kettering Cancer Center, New York, NY; Case Western University, Cleveland, OH
Address reprint requests to Kathy D. Miller, MD, Indiana University Cancer Pavilion, 535 Barnhill Dr, RT-473, Indianapolis, IN 46202; e-mail: kathmill{at}iupui.edu
PURPOSE: This randomized phase III trial compared the efficacy and safety of capecitabine with or without bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane.
PATIENTS AND METHODS: Patients were randomly assigned to receive capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks, alone or in combination with bevacizumab (15 mg/kg) on day 1. The primary end point was progression-free survival (PFS), as determined by an independent review facility.
RESULTS: From November 2000 to March 2002, 462 patients were enrolled. Treatment arms were balanced. No significant differences were found in the incidence of diarrhea, hand-foot syndrome, thromboembolic events, or serious bleeding episodes between treatment groups. Of other grade 3 or 4 adverse events, only hypertension requiring treatment (17.9% v 0.5%) was more frequent in patients receiving bevacizumab. Combination therapy significantly increased the response rates (19.8% v 9.1%; P = .001); however, this did not result in a longer PFS (4.86 v 4.17 months; hazard ratio = 0.98). Overall survival (15.1 v 14.5 months) and time to deterioration in quality of life as measured by the Functional Assessment Of Cancer TreatmentBreast were comparable in both treatment groups.
CONCLUSION: Bevacizumab was well tolerated in this heavily pretreated patient population. Although the addition of bevacizumab to capecitabine produced a significant increase in response rates, this did not translate into improved PFS or overall survival.
Supported by Genentech Inc. A full list of participating investigators and institutions can be found in the Appendix.
Presented in part at the San Antonio Breast Cancer Symposium, San Antonio, TX, December 11-14, 2002.
Authors' disclosures of potential conflicts of interest are found at the end of this article.
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