The use of bevacizumab in the modern era of targeted therapy for ovarian cancer: A systematic review and meta-analysis

Objectives. The optimal systemic therapy strategy for advanced epithelial ovarian cancer (EOC) remains unclear. We performed a systematic review and meta-analysis to assess oncologic outcomes and toxicity of bevacizumab combination treatment in advanced EOC. Methods. We conducted an electronic search of all phase 2 and 3 clinical trials involving bevacizumab combination therapy in advanced-stage EOC between 2010 and March 2020, using Embase, Medline, Epub Ahead of Print, Cochrane for clinical trials, Cochrane Database of Systematic Reviews, Web of Science and clinicaltrials. gov databases. Progression-free survival (PFS), overall survival (OS), and their hazard ratios (HR) when available were extracted. Pooled HR were calculated for each efficacy endpoint in the meta-analysis using inverse variance weighted method. Bias was assessed using the Cochrane Collaboration Risk of Bias I (ROB1) tool for randomized controlled trials. Results. Thirty-five studies were included in the qualitative analysis and eight studies in the quantitative synthesis. In the first-line setting, bevacizumab combined with chemotherapy revealed a significant improvement in PFS (pooled HR = 0.72, 95% CI 0.65-0.81) when compared to chemotherapy alone but no significant OS benefit (pooled HR = 0.88, 95% CI 0.72-1.06). In the recurrent setting, bevacizumab combinations showed significant PFS (pooled HR = 0.52, 95% CI 0.47-0.58) and OS benefits (pooled HR = 0.88, 95% CI 0.79-0.99) compared with non-bevacizumab regimens. Rate of bowel perforation was low at 1.24% (range 0-4.2%). Conclusions. Bevacizumab-containing regimens are associated with significant PFS benefit in advanced and recurrent epithelial ovarian cancer. While the difference in OS did not reach statistical significance in the first-line setting, bevacizumab was associated with improved survival in the recurrent setting. (c) 2021 Elsevier Inc. All rights reserved.