Risk of bleeding in cancer patients treated with the angiogenesis inhibitor bevacizumab: A meta-analysis

Abstract

9584 Background: Bleeding is a serious adverse event associated with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) used extensively in the treatment of cancer. Currently the overall risk of bleeding remains unclear. This study was conducted to determine the overall risk of bleeding associated with bevacizumab in cancer patients by a meta-analysis of randomized controlled trials (RCT). Methods: Databases from PUBMED and the Web Science from January 1966 until July 2008 and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences from January 2000 to through July 2008 were searched to identify relevant studies. Eligible studies included prospective RCTs in which standard anti-neoplastic therapy was administered with and without the use of bevacizumab with available data of bleeding. Summary incidence rate, relative risk (RR), and 95% confidence interval (CI) were calculated employing fixed- or random-effect models based upon the heterogeneity of the included studies. Results: A total of 13048 patients with a variety of solid tumors from 20 RCTs were included for analysis. Among patients receiving bevacizumab, the incidence of all-grade bleeding was 36.3% (95% CI: 28.0 - 45.5), and the RR was 3.1 (95% CI: 2.4 - 4.1) as compared to controls. The incidence of high grade (grade 3 or above) bleeding with bevacizumab was 2.7% (95% CI: 2.0 - 3.6%), and the RR was 1.8 (95% CI: 1.2 - 2.7). The risk of bleeding varied with the dose of bevacizumab, with RR of 3.0 (95% CI: 2.4 - 3.6) at 5mg/kg/week and 1.6 (95% CI: 1.3 - 2.0) at 2.5mg/kg/week. The risk of bleeding with bevacizumab may vary with tumor type, with higher risk seen in patients with colorectal cancer (RR=6.6, 95% CI: 3.6–12.2) and renal cell cancer (RR=3.7, 95% CI: 2.6–5.5). Bevacizumab is associated with different patterns of bleeding, with epistaxis being the most common. The incidence of all grade epistaxis with bevacizumab was 33.8% (95% CI 24.5–44.6) with a RR of 3.1 (95% CI 2.4 - 4.0). Conclusions: There is a significant increase in the risk of bleeding in cancer patients receiving bevacizumab. The risk may vary with the dose of bevacizumab and tumor type. No significant financial relationships to disclose.