Originally published as JCO Early Release 10.1200/JCO.2007.11.5154 on September 17 2007

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Randomized Phase II Study of Erlotinib Combined With Bevacizumab Compared With Bevacizumab Alone in Metastatic Renal Cell Cancer

Ronald M. Bukowski, Fairooz F. Kabbinavar, Robert A. Figlin, Keith Flaherty, Sandy Srinivas, Ulka Vaishampayan, Harry A. Drabkin, Janice Dutcher, Sarah Ryba, Qi Xia, Frank A. Scappaticci, David McDermott

From the Cleveland Clinic Foundation, Cleveland, OH; University of California at Los Angeles School of Medicine, Los Angeles; Stanford University Medical Center, Stanford; Genentech Inc, South San Francisco, CA; University of Pennsylvania, Philadelphia, PA; Wayne State University, Detroit, MI; University of Colorado Health Science Center, Aurora, CO; Our Lady of Mercy Medical Center, Bronx, NY; and Beth Israel Deaconess Medical Center, Boston, MA

Address reprint requests to Ronald M. Bukowski, MD, Cleveland Clinic Foundation, 9500 Euclid Ave, R35, Cleveland, OH 44195; e-mail: bukowsr{at}ccf.org

Purpose Bevacizumab (Bev) has clinical activity in advanced renal cell carcinoma (RCC), and, when combined with erlotinib (Erl), has shown encouraging objective response rate (ORR) and progression-free survival (PFS). We performed a phase II, randomized, double-blind, multicenter, placebo-controlled trial to assess whether Erl provides additional clinical benefit with regard to PFS and ORR when combined with Bev in first-line treatment of metastatic RCC.

Patients and Methods One hundred four patients received intravenous Bev (10 mg/kg) every 2 weeks in combination with oral Erl (150 mg) or placebo daily. Patients were treated until progression or toxicity.

Results A landmark analysis was performed 9 months after enrollment was completed (median follow-up, 9.8 months). Sixty-five patients had discontinued therapy; time to study discontinuation did not differ between the two treatment groups. The median PFS was 9.9 months (Bev + Erl [B+E]) versus 8.5 months (Bev; hazard ratio = 0.86; 95% CI, 0.5 to 1.49; P = .58). ORR (complete plus partial) was 14% (B+E) versus 13% (Bev). One complete response occurred in the B+E group. Median survival was 20 months for B+E but not reached for Bev. The most common grade 3/4 adverse events (> 5% of patients) were hypertension, rash, proteinuria, diarrhea, and hemorrhage. One treatment-related death occurred on study (GI perforation, B+E group).

Conclusion The addition of Erl to Bev was well tolerated, but did not provide additional clinical benefit compared with Bev alone. Bev has encouraging clinical activity for previously untreated metastatic RCC patients.

published online ahead of print at www.jco.org on September 17, 2007.

Supported by Genentech Inc.

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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