Bevacizumab Combination Therapy Versus Standard Chemotherapy for Ovarian Cancer in Shorter and Longer Follow-Up Duration: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT

OBJECTIVE: This systematic review and meta-analysis aims to evaluate the efficacy and safety of bevacizumab in patients with ovarian cancer over a shorter and longer follow-up period. METHODS: We searched Medline, Cochrane CENTRAL, Scopus, and Google Scholar for all phase 3 randomized controlled trials (RCTs) that administered bevacizumab to women with ovarian cancer. Review Manager 5.4 was used to calculate risk ratios (RR) and hazard ratios (HR) with 95% CIs. We assessed the quality of the included studies using version 2 of the Cochrane Risk of Bias tool (RoB 2). RESULTS: After screening the titles, abstracts, and full texts, we included nine RCTs in our systematic review and meta-analysis. Four RCTs had a low risk of bias, while 5 had some concerns. Bevacizumab was associated with a progression free survival benefit for <36 months (HR 0.59, 95% CI 0.45-0.76, P <0.0001, I2 =90%) and >36 months (HR 0.66, 95% CI 0.55-0.80, P <0.0001, I2 =80%), and an overall survival benefit for <36 months (HR 0.87, 95% CI 0.78-0.98, P =0.02, I2 =0%) but not for >36 months (HR 0.98, 95% CI 0.89-1.09, P =0.77, I2 =30%). There was no difference in deaths between intervention and control groups <36 months (RR 0.95, 95% CI 0.86-1.04, P =0.26, I2 =10%) or >36 months (RR 1.02, 95% CI 0.97-1.06, P =0.50, I2 =0%). Bevacizumab reduced disease progression <36 months (RR 0.82, 95% CI 0.72-0.92, P =0.0008, I2 =82%) but not at >36 months (RR 0.83, 95% CI 0.58-1.19, P =0.30, I2 =94%). The adverse events reported with Bevacizumab use included thrombocytopenia, neutropenia, leukocytopenia, anemia, hypertension, bleeding or hemorrhage, and gastrointestinal, cardiac, and dermatological adverse events. CONCLUSION: Bevacizumab may improve progression-free survival within and after 36 months, overall survival within 36 months, and reduce disease progression within 36 months.