Bevacizumab significantly increases the risks of hypertension and proteinuria in cancer patients: A systematic review and comprehensive meta-analysis

Published data regarding the overall risks and incidence of hypertension and proteinuria associated with bevacizumab were still unclear. To quantify the precise risks and incidence, we performed this comprehensive meta-analysis of 72 published clinical trials including 21902 cases and 20608 controls. The overall incidence, risk ratios (RRs), and 95% confidence intervals (95% CIs) were calculated using a fixed or random-effect model based on the heterogeneity. The incidence of all-grade and high-grade hypertension were 25.3% (95% CI: 21.5%−29.5%) and 8.2% (95% CI: 7%−9.8%) for patients treated with bevacizumab. And the incidence of all-grade and high-grade proteinuria were 18% (95% CI: 11.7%−26.6%) and 2.4% (95% CI: 1.8%−3.2%), respectively. Compared with controls, bevacizumab significantly increased the risks of all-grade (RR: 3.595, 95% CI: 2.952−4.378) and high-grade hypertension (RR: 5.173, 95% CI: 4.188−6.390). Obviously increased risks of all-grade (RR: 3.369, 95% CI: 2.492−4.556) and high-grade proteinuria (RR: 5.494, 95% CI: 3.991−7.564) were also observed. In the subgroup analysis, the risks of hypertension and proteinuria may significantly vary with bevacizumab dosage, cancer types and concomitant drugs. Whereas, no obvious difference were discovered when stratified based on phase of trials, age of patients, treatment line and duration. So, close monitor and effective management were highly recommended for the safe use of bevacizumab.