Risk of Thrombo-Embolic Events in Ovarian Cancer: Does Bevacizumab Tilt the Scale? A Systematic Review and Meta-Analysis.

Thromboembolic events are the second cause of death in cancer patients. In ovarian cancer, 3-10% of patients present with venous thromboembolism (VTE), but the incidence may rise to 36% along the disease course. Bevacizumab is a monoclonal antibody directed against vascular endothelial-derived growth factor, and in in vitro studies it showed a predisposition to hemostasis perturbation, including thrombosis. However, in vivo and clinical studies have shown conflicting results for its use as a treatment for ovarian cancer, so we conducted a systematic review and meta-analysis on the risk of arterial thromboembolism (ATE) and VTE in ovarian cancer patients treated with bevacizumab. The review comprised 14 trials with 6221 patients: ATE incidence was reported in 5 (4811 patients) where the absolute risk was 2.4% with bevacizumab vs. 1.1% without (RR 2.45; 95% CI 1.27-4.27, p = 0.008). VTE incidence was reported in 9 trials (5121 patients) where the absolute risk was 5.4% with bevacizumab vs. 3.7% without (RR 1.32; 95% CI 1.02-1.79, p = 0.04). Our analysis showed that the risk of arterial and venous thromboembolism increased in patients treated with bevacizumab. Thrombolic events (TEs) are probably underreported, and studies should discriminate between ATE and VTE. Bevacizumab can be considered as an additional risk factor when selecting patients for primary prophylaxis with anticoagulants.