An Updated Meta-Analysis of Fatal Adverse Events Caused by Bevacizumab Therapy in Cancer Patients

Background: The risk of fatal adverse events (FAEs) due to bevacizumab-based chemotherapy has not been well described; we carried out an updated meta-analysis regarding this issue. Methods: An electronic search of Medline, Embase and The Cochrane Central Register of Controlled Trials was conducted to investigate the effects of randomized controlled trials on bevacizumab treatment on cancer patients. Random or fixed-effect meta-analytical models were used to evaluate the risk ratio (RR) of FAEs due to the use of bevacizumab. Results: Thirty-four trials were included. Allocation to bevacizumab therapy significantly increased the risk of FAEs; the RR was 1.29 (95% CI:1.05–1.57). This association varied significantly with tumor types (P = 0.002) and chemotherapeutic agents (P = 0.005) but not with bevacizumab dose (P = 0.90). Increased risk was seen in patients with non–small cell lung cancer, pancreatic cancer, prostate cancer, and ovarian cancer. However, FAEs were lower in breast cancer patients treated with bevacizumab. In addition, bevacizumab was associated with an increased risk of FAEs in patients who received concomitant agents of taxanes and/or platinum. Conclusion: Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs among patients with special tumor types, particularly when combined with chemotherapeutic agents such as platinum.