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Robert J. Motzer, MD; Brian I. Rini, MD; Ronald M. Bukowski, MD; Brendan D. Curti, MD; Daniel J. George, MD; Gary R. Hudes, MD; Bruce G. Redman, DO; Kim A. Margolin, MD; Jaime R. Merchan, MD; George Wilding, MD; Michelle S. Ginsberg, MD; Jennifer Bacik, MS; Sindy T. Kim, BS; Charles M. Baum, MD, PhD; M. Dror Michaelson, MD, PhD

JAMA. 2006;295:2516-2524.

Context  Current treatment options for metastatic renal cell carcinoma (RCC) are limited and there is a need to identify novel and effective therapies. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, which has shown activity in an initial study of cytokine-refractory metastatic RCC patients.

Objective  To confirm the antitumor efficacy of sunitinib as second-line treatment in patients with metastatic clear-cell RCC, the predominant cell type of this malignancy.

Design, Setting, and Patients  Open-label, single-arm, multicenter clinical trial. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The reported data apply through August 2005. Patients (N = 106) had metastatic clear-cell RCC, which had progressed despite previous cytokine therapy.

Intervention  Repeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle.

Main Outcome Measures  Assessment of clinical response, degree of tumor regression on imaging studies using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Primary end point was overall objective response rate (complete plus partial). Secondary end points were progression-free survival and safety. Response was evaluated by independent third-party core imaging laboratory and by treating physicians (investigator assessment).

Results  All 106 patients received sunitinib and were included in the intent-to-treat population for safety analyses. Of these, 105 patients were evaluable for efficacy analyses. The objective response rate according to an independent third-party assessment resulted in 36 patients with partial response (34%; 95% confidence interval, 25%-44%), and a median progression-free survival of 8.3 months (95% confidence interval, 7.8-14.5 months). The most common adverse events experienced by patients were fatigue in 30 (28%) and diarrhea 21 (20%). Neutropenia, elevation of lipase, and anemia were the most common laboratory abnormalities observed in 45 (42%), 30 (28%), and 27 (26%) patients, respectively.

Conclusion  The results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC.

Trial Registration  clinicaltrials.gov Identifier: NCT00077974

Author Affiliations: Departments of Medicine (Dr Motzer), Radiology (Dr Ginsberg), and Biostatistics and Epidemiology (Ms Bacik), Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Medicine, University of California, San Francisco (Dr Rini); Experimental Therapeutics Program, Cleveland Clinic Foundation, Cleveland, Ohio (Dr Bukowski); The Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Portland, Ore (Dr Curti); Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC (Dr George); Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pa (Dr Hudes); Department of Internal Medicine, University of Michigan, Ann Arbor (Dr Redman); Division of Medical Oncology, City of Hope National Medical Center, Duarte, Calif (Dr Margolin); Department of Oncology, Mayo Clinic, Rochester, Minn (Dr Merchan); Department of Medicine, University of Wisconsin Comprehensive Cancer Center, Madison (Dr Wilding); Oncology Clinical Development, Pfizer Inc, La Jolla, Calif (Ms Kim and Dr Baum); Department of Hematology/Oncology, Massachusetts General Hospital, Boston (Dr Michaelson). Dr Rini is now with the Cleveland Clinic Foundation, Cleveland, Ohio.

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