Originally published as JCO Early Release 10.1200/JCO.2006.09.7535 on July 2 2007

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Phase II Clinical Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, As First-Line Therapy in Patients With Metastatic Breast Cancer Previously Treated With Anthracycline Chemotherapy

Henri Roché, Louise Yelle, Francesco Cognetti, Louis Mauriac, Craig Bunnell, Joseph Sparano, Pierre Kerbrat, Jean-Pierre Delord, Linda Vahdat, Ronald Peck, David Lebwohl, Rana Ezzeddine, Hervé Curé

From the Institut Claudius Regaud, Toulouse; Institut Bergonie, Bordeaux; Centre Eugene Marquis, Rennes; Centre Jean Perrin, Clermont-Ferrand, France; Centre Hospitalier de l'Université de Montréal–Hôpital Notre-Dame, Montreal, Quebec, Canada; Comitato Etico (Istituto di Ricovero e Cura a Carattere Scientifico) di Roma, IFO-Istituto Regina Elena, Rome, Italy; Dana-Farber Cancer Institute, Boston, MA; Albert Einstein Comprehensive Cancer Center, Montefiore Medical Center, Department of Oncology; Weill Medical College of Cornell University, New York, NY; and Bristol-Myers Squibb, Wallingford, CT

Address reprint requests to Henri Roché, MD, Institut Claudius Regaud, 20-24 rue du Saint Pierre, 31052 Toulouse Cedex, France; e-mail: roche.henri{at}claudiusregaud.fr

Purpose: There is a need for new agents to treat metastatic breast cancer (MBC) in patients for whom anthracycline therapy has failed or is contraindicated. This study was conducted to assess the efficacy and safety of the novel antineoplastic, the epothilone B analog ixabepilone, in patients with MBC previously treated with an adjuvant anthracycline.

Patients and Methods: Patients were age 18 years and had received a prior anthracycline-based regimen as adjuvant treatment. Ixabepilone as first-line metastatic chemotherapy was administered as a 40 mg/m² intravenous infusion during 3 hours every 3 weeks. The primary efficacy end point was objective response rate (ORR). Secondary efficacy end points included duration of response, time to response, time to progression, and survival.

Results: All 65 patients were assessable for response. Their median age was 52 years (range, 33 to 80 years). ORR was 41.5% (95% CI, 29.4% to 54.4%), median duration of response was 8.2 months (95% CI, 5.7 to 10.2 months), and median time to response was 6 weeks (range, 5 to 17 weeks). Median survival was 22.0 months (95% CI, 15.6 to 27.0 months). Treatment-related adverse events were manageable and mostly grades 1/2: the most common of these (other than alopecia) was mild to moderate neuropathy, which was primarily sensory and mostly reversible in nature.

Conclusion: Ixabepilone is efficacious and has a predictable and manageable safety profile in women with MBC previously treated with an adjuvant anthracycline.

published online ahead of print at www.jco.org on July 31, 2006.

Supported by Bristol-Myers Squibb Co.

Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, May 18-21, 2002, Orlando, FL; 39th Annual Meeting of the American Society of Clinical Oncology, May 31-June 3, 2003, Chicago, IL; International Union Against Cancer Meeting, 2006; and Roché H, Perez E, Llombart-Cussac A, et al: Ixabepilone, an epothilone analog, is effective in ER-, PR-, HER2-negative (triple-negative) patients: data from neoadjuvant and metastatic breast cancer trials. Ann Oncol 17:ix93-ix113, 2006 (abstr 256-P).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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