Bevacizumab combined with chemotherapy for ovarian cancer: an updated systematic review and meta-analysis of randomized controlled trials

Background: This meta-analysis was updated with results from a new trial and final data to reassess the efficacy and safety of bevacizumab combined with chemotherapy in ovarian cancer (OC). Methods: Randomized controlled trials (RCTs) were searched in PubMed, EMBASE, Cochrane clinical trials, Web of Science and clinicaltrial.gov databases. Outcomes included the progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and common adverse events. The hazard ratio (HR), risk ratio (RR) and odds ratio (OR) were pooled when the meta-analysis was performed. Results: Five RCTs with 4994 patients were included. In overall newly diagnosed OC, bevacizumab combined with chemotherapy did not significantly improve PFS (HR 0.85, 95%CI 0.70-1.02) or OS (HR 0.94, 95%CI 0.84-1.05). In the high-risk progression subgroup, the addition of bevacizumab significantly improved PFS (HR 0.76, 95%CI 0.68-0.84) and OS (HR 0.85, 95%CI 0.74-0.96). In recurrent OC, the addition of bevacizumab to chemotherapy significantly extended PFS (HR 0.53, 95%CI 0.45-0.63) and OS (HR 0.87, 95%CI 0.77-0.99). The ORR was improved (OR 2.37, 95%CI 1.99-2.82) in the overall population. Bevacizumab increased the incidence of hypertension (RR 21.27, 95%CI 9.42-48.02), proteinuria (RR 4.77, 95%CI 2.15-10.61), bleeding (RR 3.16, 95%CI 1.59-6.30), GI perforations (RR 2.76, 95%CI 1.51-5.03), arterial thrombosis events (RR 2.39, 95%CI 1.39-4.10) and venous thrombosis events (RR 1.43, 95%CI 1.04-1.96). Conclusions: Bevacizumab combined with chemotherapy significantly improved PFS and OS in both patients with high-risk of progression and patients with recurrent OC, with an increased incidence of common adverse events. However, no statistically significant survival benefit was identified in the front-line settings.