Originally published as JCO Early Release 10.1200/JCO.2007.12.6557 on October 29 2007
Journal of Clinical Oncology, Vol 25, No 33 (November 20), 2007: pp. 5210-5217
© 2007 American Society of Clinical Oncology.
Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment
Eva S. Thomas,
Henry L. Gomez,
Rubi K. Li,
Hyun-Cheol Chung,
Luis E. Fein,
Valorie F. Chan,
Jacek Jassem,
Xavier B. Pivot,
Judith V. Klimovsky,
Fernando Hurtado de Mendoza,
Binghe Xu,
Mario Campone,
Guillermo L. Lerzo,
Ronald A. Peck,
Pralay Mukhopadhyay,
Linda T. Vahdat,
Henri H. Roché
From the M.D. Anderson Cancer Center, Houston, TX; Instituto Nacional de Enfermedades Neoplasicas; Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru; St Luke's Medical Center; Veterans Memorial Medical Center, Quezon City, Philippines; Yonsei Cancer Center, Seoul, Republic of Korea; Centro de Oncologia Rosario, Sante Fe; Hospital de Oncologia ‘Maria Curie,’ Buenos Aires, Argentina; Medical University of Gdansk, Gdansk, Poland; C.H.U. Jean Minjoz, Besançon; Centre Rene Gauducheau, Nantes; Institut Claudius Regaud, Toulouse, France; Bristol-Myers Squibb, Research and Development, Wallingford, CT; Cancer Hospital –Chinese Academy of Medical Sciences, Beijing, China; and Weill Medical College of Cornell University, New York, NY
Address reprint requests to Eva S. Thomas, MD, 280 West MacArthur Blvd, Oakland, CA 94611; e-mail: eva.s.thomas{at}kp.org
Purpose Effective 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 Methods Seven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m2 intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m2 orally on days 1 through 14 of a 21-day cycle, or capecitabine alone 2,500 mg/m2 on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review.
Results Ixabepilone 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.
Conclusion Ixabepilone plus capecitabine demonstrates superior efficacy to capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.
published online ahead of print at www.jco.org on October 29, 2007.
Supported by Bristol-Myers Squibb. Interim efficacy and safety analyses were supervised by an independent data-monitoring committee. The authors vouch for the completeness and accuracy of results presented.
Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 3, 2007, Chicago, IL.
Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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