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

Objective: This 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.

Methods: The 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).

Results: Eight 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).

Conclusion: Current 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.