Increased Risk of Serious Hemorrhage with Bevacizumab in Cancer Patients: A Meta-Analysis

Background: The role of the widely-used angiogenesis inhibitor bevacizumab in the development of serious hemorrhage is not well defined in cancer patients. This study was conducted to determine the overall risk of hemorrhage with bevacizumab by a systematic review and meta-analysis of randomized controlled trials (RCT). Methods: Databases from PubMed and the Web of Science from January 1966 to May 2009 and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences from January 2000 to May 2009 were searched to identify relevant studies. Eligible studies included prospective RCTs in which bevacizumab was compared to controls concurrently with antineoplastic therapy. Summary incidence rates, relative risks (RR), and 95% confidence intervals (CI) were calculated employing fixed-or random-effects models. Results: A total of 12,617 patients with a variety of solid tumors from 20 RCTs were included for analysis. The incidence of all-grade hemorrhage was 30.4% (95% CI 21.5-40.9), with 3.5% (95% CI 2.2-5.7%) being high grade (grade 3-5). Overall, bevacizumab significantly increased the risk of bleeding with an RR of 2.48 (95% CI 1.93-3.18) when compared to the controls, with RRs of 3.02 (95% CI 2.42-3.78) and 2.01 (95% CI 1.43-2.83) at 5 and 2.5 mg/kg/week, respectively. Significantly increased risks for epistaxis or pulmonary hemorrhage were observed. In addition, bevacizumab significantly increased the risk of high-grade bleeding with an RR of 1.91 (95% CI 1.36-2.68). The risk of fatal bleeding was low (0.8%; 95% CI 0.4-1.7), and significantly elevated only in lung cancer (RR 5.02; 95% CI 1.52-16.66). Conclusion: Bevacizumab may significantly increase the risk of serious hemorrhage in cancer patients. Copyright (C) 2010 S. Karger AG, Basel