Comparative Efficacy and Safety of Poly (ADP-Ribose) Polymerase Inhibitors in Patients With Ovarian Cancer: A Systematic Review and Network Meta-Analysis

Abstract

ObjectiveThis study aims to compare the efficacy and safety of different poly (ADP-ribose) polymerase (PARP) inhibitors in patients with ovarian cancer through a network meta-analysis to support clinical treatment choices.MethodsThe Cochrane Library, PubMed, Embase, Science Citation Index, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chongqing VIP (CQVIP), and Chinese BioMedical Literature Database (CBM) were searched with a cutoff date of 14 January 2021. ClinicalTrials.gov was also checked for supplementary data. Phase II or III randomized controlled trials that compared a PARP inhibitor with a placebo in patients with relapsed or newly diagnosed advanced ovarian cancer were included. The hazard ratios (HRs) for progression-free survival and overall survival and odds ratios (ORs) for grade 3 or higher adverse events were analyzed. The network meta-analysis was conducted in a Bayesian framework based on the Markov Chain Monte Carlo model in the R gemtc package (version 4.0.3).ResultsEight eligible articles reporting six trials with a total of 2,801 patients were incorporated in this network meta-analysis. Three trials compared olaparib with placebo. Two trials compared niraparib with placebo. One trial compared rucaparib with placebo. The network meta-analysis failed to show significant differences in progression-free survival among the three PARP inhibitors: HR of 0.64, 95% confidence interval of 0.3 to 1.42 for olaparib versus niraparib, and olaparib versus rucaparib (0.86; 0.33 to 2.33). The comparison between niraparib and rucaparib also did not express a statistical difference (1.34; 0.47 to 3.72). Subgroup analysis bybreast cancer susceptibility gene (BRCA) status showed no obvious difference in progression-free survival among the three PARP inhibitors regardless of BRCA mutation status. Olaparib had fewer grade 3 or higher adverse events than niraparib (OR, 0.27; 95% confidence interval, 0.13 to 0.55) and rucaparib (0.34; 0.14 to 0.86). However, the analysis failed to show a significant difference between niraparib and rucaparib (1.27; 0.49 to 3.27).ConclusionCurrent evidence indicates that there is no significant difference observed in efficacy among olaparib, niraparib, and rucaparib. However, olaparib might have fewer grade 3 or higher adverse events.