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

BackgroundThe clinical background of cancer patients is complex, and the efficacy and safety of different poly (ADP-ribose) polymerase inhibitors (PARPis) vary greatly. Therefore, we conducted a systematic review and network meta-analysis to compare the efficacy and safety of the six PARPis and systematically evaluated the differences in PARPis in the relevant clinical contexts. MethodsDatabases (PubMed, Cochrane, Embase, etc.) were searched from Jan 1, 1980 to Oct 20, 2023, for randomized clinical trials. The overall survival (OS), progression-free survival (PFS), and grade 3-5 adverse events (AEs) were the main outcomes and measures. ResultsForty-seven trials targeting 17 300 patients comparing six different PARPis. Talazoparib was associated with the highest PFS (HR = 0.59, 95% CI: 0.52-0.68), accompanied by grade 3-5 AEs (HR = 4.96, 95% CI: 1.49-18.08). There were additional potential beneficial relationships in populations: homologous recombination deficiency (HRD) with PFS (HR = 0.34, 95% CI: 0.24-0.43); BRCA gene mutations with OS (HR = 0.79, 95% CI: 0.68-0.93) and PFS (HR = 0.30, 95% CI: 0.27-0.34); new diagnoses with OS (HR = 0.79, 95% CI: 0.61-0.97); and sensitivity to prior platinum therapy with PFS (HR = 0.43, 95% CI: 0.39-0.47). ConclusionPARPis are more effective in HRD, newly diagnosed or platinum-sensitive cancer populations, and talazoparib is recommended as the first choice.