Originally published as JCO Early Release 10.1200/JCO.2008.16.9847 on October 20 2008

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Bevacizumab Plus Interferon Alfa Compared With Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: CALGB 90206

Brian I. Rini, Susan Halabi, Jonathan E. Rosenberg, Walter M. Stadler, Daniel A. Vaena, San-San Ou, Laura Archer, James N. Atkins, Joel Picus, Piotr Czaykowski, Janice Dutcher, Eric J. Small

From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Department of Biostatistics and Bioinformatics, Duke University Medical Center, and Cancer and Leukemia Group B Statistical Center, Durham; Southeast Cancer Control Consortium Inc, Winston-Salem, NC; University of California at San Francisco, San Francisco, CA; University of Chicago Medical Center, Chicago, IL; University of Iowa, Iowa City, IA; Washington University, St Louis, MO; CancerCare Manitoba, Winnipeg, Manitoba, and the National Cancer Institute Canada Clinical Trials Group, Kingston, ON, Canada; New York Medical College, New York, NY; and the Eastern Cooperative Oncology Group, Boston, MA

Corresponding author: Brian I. Rini, MD, Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave, Desk R35, Cleveland, OH 44195; e-mail: rinib2{at}ccf.org

Purpose Bevacizumab is an antibody that binds to vascular endothelial growth factor (VEGF) and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN) is a historic standard first-line treatment for RCC. A prospective, randomized phase III trial of bevacizumab plus IFN versus IFN monotherapy was conducted.

Patients and Methods Patients with previously untreated, metastatic clear-cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN (9 million U subcutaneously three times weekly) or the same dose and schedule of IFN monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate (ORR), and safety.

Results Between October 2003 and July 2005, 732 patients were enrolled. The prespecified stopping rule for OS has not yet been reached. The median PFS was 8.5 months in patients receiving bevacizumab plus IFN (95% CI, 7.5 to 9.7 months) versus 5.2 months (95% CI, 3.1 to 5.6 months) in patients receiving IFN monotherapy (log-rank P < .0001). The adjusted hazard ratio was 0.71 (95% CI, 0.61 to 0.83; P < .0001). Bevacizumab plus IFN had a higher ORR as compared with IFN (25.5% [95% CI, 20.9% to 30.6%] v 13.1% [95% CI, 9.5% to 17.3%]; P < .0001). Overall toxicity was greater for bevacizumab plus IFN, including significantly more grade 3 hypertension (9% v 0%), anorexia (17% v 8%), fatigue (35% v 28%), and proteinuria (13% v 0%).

Conclusion Bevacizumab plus IFN produces a superior PFS and ORR in untreated patients with metastatic RCC as compared with IFN monotherapy. Toxicity is greater in the combination therapy arm.

published online ahead of print at www.jco.org on October 20, 2008.

Supported in part by grants from the National Cancer Institute to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chair; Grant No. CA31946); to the Cancer and Leukemia Group B Statistical Center (Stephen George, PhD; Grant No. CA33601); and by Grants No. CA33601 (S.H.), CA60138 (J.E.R.), CA41287 (W.M.S.), CA47642 (D.A.V.), CA45808 (J.N.A.), and CA77440 (J.P.).

The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.

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

Clinical trial information can be found for the following: NCT00072046 [ClinicalTrials.gov] .

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