Risks of Proteinuria and Hypertension With Bevacizumab, an Antibody Against Vascular Endothelial Growth Factor: Systematic Review and Meta-Analysis

Background Angiogenesis inhibitors have emerged as an effective targeted therapy in the treatment of patients with many cancers. One of the most widely used angiogenesis inhibitors is bevacizumab, a neutralizing antibody against vascular endothelial growth factor. The overall risk of proteinuria and hypertension in patients with cancer on bevacizumab therapy is unclear. We performed a systematic review and meta-analysis of published clinical trials of bevacizumab to quantify the risk of proteinuria and hypertension. Methods The databases MEDLINE (OVID, 1966 to June 2006) and Web of Science and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2006 were searched to identify relevant studies. Eligible studies were randomized controlled trials of patients with cancer treated with bevacizumab that described the incidence of proteinuria and hypertension. Relative risk (RR) was calculated by using the fixed-effects model. Results A total of 1,850 patients were included in the 7 trials identified from the literature. Bevacizumab was associated with a significant increased risk of proteinuria (RR, 1.4 with low-dose bevacizumab; 95% confidence interval [CI], 1.1 to 1.7; RR, 2.2 with high dose; 95% CI, 1.6 to 2.9). Hypertension also was increased significantly among patients receiving bevacizumab (RR, 3.0 for low dose; 95% CI, 2.2 to 4.2; RR, 7.5 for high dose; 95% CI, 4.2 to 13.4). Conclusion There was a significant dose-dependent increase in risk of proteinuria and hypertension in patients with cancer who received bevacizumab. Angiogenesis inhibitors have emerged as an effective targeted therapy in the treatment of patients with many cancers. One of the most widely used angiogenesis inhibitors is bevacizumab, a neutralizing antibody against vascular endothelial growth factor. The overall risk of proteinuria and hypertension in patients with cancer on bevacizumab therapy is unclear. We performed a systematic review and meta-analysis of published clinical trials of bevacizumab to quantify the risk of proteinuria and hypertension. The databases MEDLINE (OVID, 1966 to June 2006) and Web of Science and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2006 were searched to identify relevant studies. Eligible studies were randomized controlled trials of patients with cancer treated with bevacizumab that described the incidence of proteinuria and hypertension. Relative risk (RR) was calculated by using the fixed-effects model. A total of 1,850 patients were included in the 7 trials identified from the literature. Bevacizumab was associated with a significant increased risk of proteinuria (RR, 1.4 with low-dose bevacizumab; 95% confidence interval [CI], 1.1 to 1.7; RR, 2.2 with high dose; 95% CI, 1.6 to 2.9). Hypertension also was increased significantly among patients receiving bevacizumab (RR, 3.0 for low dose; 95% CI, 2.2 to 4.2; RR, 7.5 for high dose; 95% CI, 4.2 to 13.4). There was a significant dose-dependent increase in risk of proteinuria and hypertension in patients with cancer who received bevacizumab.