Originally published as JCO Early Release 10.1200/JCO.2007.14.5375 on March 17 2008

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Phase II Study of Sunitinib Malate, an Oral Multitargeted Tyrosine Kinase Inhibitor, in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

Harold J. Burstein, Anthony D. Elias, Hope S. Rugo, Melody A. Cobleigh, Antonio C. Wolff, Peter D. Eisenberg, Mary Lehman, Bonne J. Adams, Carlo L. Bello, Samuel E. DePrimo, Charles M. Baum, Kathy D. Miller

From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Health Sciences Center, Denver, CO; University of California San Francisco, San Francisco; California Cancer Care Inc, Greenbrae; Pfizer Inc, La Jolla; TRACON Pharmaceuticals Inc, San Diego, CA; Rush University Medical Center, Chicago, IL; Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD; and the Indiana University Simon Cancer Center, Indianapolis, IN

Corresponding author: Harold J. Burstein, MD, PhD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA, 02115; e-mail: hburstein{at}partners.org

Purpose: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC).

Patients and Methods: Sixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis.

Results: Seven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11%. Three additional patients (5%) maintained stable disease for 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required dose interruption during 1 cycle, and 25 patients required dose reduction (39%). Thirty-six patients (56%) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions.

Conclusion: Sunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted.

published online ahead of print at www.jco.org on March 17, 2008.

Supported by Pfizer Inc.

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