Originally published as JCO Early Release 10.1200/JCO.2005.00.232 on May 2 2005

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Combined Analysis of Efficacy: The Addition of Bevacizumab to Fluorouracil/Leucovorin Improves Survival for Patients With Metastatic Colorectal Cancer

From the University of California Los Angeles, Los Angeles; Genentech Inc, South San Francisco; University of California San Francisco, San Francisco, CA; Duke University, Durham, NC

Address reprint requests to Somnath Sarkar, PhD, Medical Affairs, Genentech Inc, One DNA Way, South San Francisco, CA 94080; e-mail: sarkar.somnath{at}gene.com

PURPOSE: Bevacizumab (Avastin; Genentech Inc, South San Francisco, CA), a recombinant, humanized anti–vascular endothelial growth factor monoclonal antibody that inhibits tumor angiogenesis, has demonstrated survival benefit in patients with previously untreated metastatic colorectal cancer when combined with irinotecan/fluourouracil (FU)/leucovorin (LV; IFL). Three randomized clinical studies have evaluated bevacizumab in combination with FU/LV alone. A combined analysis of raw data from these studies was performed to better assess the efficacy of bevacizumab with FU/LV.

PATIENTS AND METHODS: The analysis used primary efficacy data from three independent studies, including 241 patients in a combined control group receiving either FU/LV or IFL and 249 patients receiving FU/LV/bevacizumab (5 mg/kg once every 2 weeks). The efficacy data included response rate, progression-free survival, and overall survival.

RESULTS: The median duration of survival was 17.9 months in the FU/LV/bevacizumab group, compared with 14.6 months in the combined control group, corresponding to a hazard ratio for death of 0.74 (P = .008). The median duration of progression-free survival was 8.8 months in the FU/LV/bevacizumab group, compared with 5.6 months in the combined control group, corresponding to a hazard ratio for disease progression of 0.63 (P .0001). The addition of bevacizumab also improved the response rate (34.1% v 24.5%; P = .019).

CONCLUSION: The addition of bevacizumab to FU/LV provides a statistically significant and clinically relevant benefit to patients with previously untreated metastatic colorectal cancer.

Supported by Genentech Inc.

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

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

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