A comprehensive comparison of PARP inhibitors as maintenance therapy in platinum-sensitive recurrent ovarian cancer: a systematic review and network meta-analysis.

Abstract

Background: PARP inhibitors (PARPis) have shown promising effectiveness for ovarian cancer. This network meta-analysis (PROSPERO registration number CRD42024503390) comprehensively evaluated the effectiveness and safety of PARPis in platinum-sensitive recurrent ovarian cancer (PSROC).

Methods: Articles published before January 6, 2024 were obtained from electronic databases. The study assessed and compared survival outcomes including overall survival (OS), progression-free survival (PFS), second progression-free survival (PFS2), time to first subsequent treatment (TFST), time to second subsequent treatment (TSST), and chemotherapy-free interval (CFI). Additionally, safety outcomes were investigated, specifically focusing on grade 3-4 treatment-emergent adverse effects (TEAEs). The evaluation of OS and PFS was also conducted based on the BRCA and HRD (homologous recombination deficiency) statuses.

Results: Six randomized controlled trials were examined and the four PARPis (olaparib, niraparib, rucaparib and fuluzolparib) have been found to significantly increase the PFS in entire population as well as in subgroups of HRD and BRCAm (BRCA mutation). Only olaparib demonstrated a substantial improvement in OS compared to placebo in entire population (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.60-0.90), as well as in the subgroup of BRCAm. All analyzed PARPis had significant efficacy in prolonging PFS2, TFST, TSST and CFI. For safety concerns, PARPis could significantly increase incidence of TEAEs (grade3-4), while olaparib had least haematological TEAEs (grade3-4) events compared to other PARPis.

Conclusion: All included PARPis showed various degrees of benefit in survival outcomes and safety profile was acceptable for PSROC patients. Among them olaparib had the best performance in both efficacy and safety.