Originally published as JCO Early Release 10.1200/JCO.2006.09.3849 on July 2 2007

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Efficacy and Safety of Ixabepilone (BMS-247550) in a Phase II Study of Patients With Advanced Breast Cancer Resistant to an Anthracycline, a Taxane, and Capecitabine

Edith A. Perez, Guillermo Lerzo, Xavier Pivot, Eva Thomas, Linda Vahdat, Linda Bosserman, Patrice Viens, Can Cai, Brian Mullaney, Ronald Peck, Gabriel N. Hortobagyi

From the Department of Hematology and Oncology, Mayo Clinic, Jacksonville, FL; Division of Oncology, Hospital de Oncologia Maria Curie, Ciudad de Buenos Aires, Argentina; Division of Oncology, Centre Hospitalier Universitaire de Besançon, Besançon, France; Departments of Medicine and Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Department of Medicine, Weill Cornell Breast Center, New York, NY; Department of Medical Oncology and Hematology, Wilshire Oncology Medical Group Inc, La Verne, CA; Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France; and Oncology Research, Bristol-Myers Squibb, Wallingford, CT

Address reprint requests to Edith A. Perez, MD, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224; e-mail: Perez.edith{at}mayo.edu

Purpose: To evaluate the efficacy and safety of ixabepilone in patients with metastatic breast cancer (MBC) resistant to anthracycline, taxane, and capecitabine, in this multicenter, phase II study.

Patients and Methods: Patients with measurable disease who had tumor progression while receiving prior anthracycline, taxane, and capecitabine were enrolled. Ixabepilone 40 mg/m² monotherapy was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle. The primary end point was objective response rate (ORR), assessed by an independent radiology facility (IRF).

Results: A total of 126 patients were treated and 113 were assessable for response. Patients were heavily pretreated: 88% had received at least two lines of prior chemotherapy in the metastatic setting. IRF-assessed ORR was 11.5% (95% CI, 6.3% to 18.9%) for response-assessable patients. Investigator-assessed ORR for all treated patients was 18.3% (95% CI, 11.9% to 26.1%). Fifty percent of patients achieved stable disease (SD); 14.3% achieved SD 6 months. Median duration of response and progression-free survival were 5.7 and 3.1 months, respectively. Median overall survival was 8.6 months. Patients received a median of 4.0 treatment cycles (range, one to 16 cycles), and 25% of patients received eight cycles. Grade 3/4 treatment-related events included peripheral sensory neuropathy (14%), fatigue/asthenia (13%), myalgia (8%), and stomatitis/mucositis (6%). Resolution of grade 3/4 peripheral sensory neuropathy occurred after a median period of 5.4 weeks.

Conclusion: Ixabepilone demonstrated clear activity and a manageable safety profile in patients with MBC resistant to anthracycline, taxane, and capecitabine. Responses were durable and notable in patients who had not previously responded to multiple prior therapies.

published online ahead of print at www.jco.org on July 2, 2007.

Supported by Bristol-Myers Squibb Co (study and editorial).

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

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

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