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Multicenter, Phase II Trial of Sunitinib in Previously Treated, Advanced Non–Small-Cell Lung Cancer

Mark A. Socinski, Silvia Novello, Julie R. Brahmer, Rafael Rosell, Jose M. Sanchez, Chandra P. Belani, Ramaswamy Govindan, James N. Atkins, Heidi H. Gillenwater, Cinta Pallares, Lesley Tye, Paulina Selaru, Richard C. Chao, Giorgio V. Scagliotti

From the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill; Southeastern Medical Oncology Center, Oncology, Goldsboro, NC; Johns Hopkins University, School of Medicine, Baltimore, MD; University of Pittsburgh School of Medicine, Pittsburgh, PA; Washington University, School of Medicine, St Louis, MO; University of Virginia, Department of Internal Medicine, Charlottesville, VA; Pfizer Inc, Global Research and Development, La Jolla, CA; University of Turin, Department of Clinical and Biological Sciences, Orbassano (Turin), Italy; Catalan Institute of Oncology, Barcelona; and Hospital de San Pablo, Oncology, Barcelona, Spain

Corresponding author: Mark A. Socinski, MD, Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, CB# 7305, Chapel Hill, NC 27599; e-mail: socinski{at}med.unc.edu

Purpose Aberrant vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) signaling have been shown to play a role in non–small-cell lung cancer (NSCLC) pathogenesis and are associated with decreased survival. We evaluated the clinical activity and tolerability of sunitinib malate (SU11248), an oral, multitargeted tyrosine kinase inhibitor that blocks the activity of receptors for VEGF and PDGF, as well as related tyrosine kinases in patients with previously treated, advanced NSCLC.

Patients and Methods Patients with stage IIIB or IV NSCLC for whom platinum-based chemotherapy had failed received 50 mg/d of sunitinib for 4 weeks followed by 2 weeks of no treatment in 6-week treatment cycles. The primary end point was objective response rate (ORR); secondary end points included progression-free survival, overall survival, and safety.

Results Of the 63 patients treated with sunitinib, seven patients had confirmed partial responses, yielding an ORR of 11.1% (95% CI, 4.6% to 21.6%). An additional 18 patients (28.6%) experienced stable disease of at least 8 weeks in duration. Median progression-free survival was 12.0 weeks (95% CI, 10.0 to 16.1 weeks), and median overall survival was 23.4 weeks (95% CI, 17.0 to 28.3 weeks). Therapy was generally well tolerated.

Conclusion Sunitinib has promising single-agent activity in patients with recurrent NSCLC, with an ORR similar to that of currently approved agents and an acceptable safety profile. Further evaluation in combination with other targeted agents and chemotherapy in patients with NSCLC is warranted.

This study was supported by funding from Pfizer Inc.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; the 8th Annual Lung Cancer Conference, June 27-30, 2007, Maui, HI; the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006 Atlanta, GA (Proc Am Soc Clin Oncol 24:364s, 2006 [abstr 7001]); and the 31st European Society for Medical Oncology Congress, September 29-October 3, 2006, Istanbul, Turkey.

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

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