Efficacy of Poly(ADP-ribose) Polymerase Inhibitors According to Clinical Risk in Newly Diagnosed, Advanced Ovarian Cancer: A Meta-analysis of Phase III Clinical Trials
Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy improves progression-free survival (PFS) in patients with advanced ovarian cancer, with greatest benefit observed in patients with BRCA alterations and homologous recombination deficiencies (HRD). This study evaluated PFS benefit of PARP inhibitors according to clinically relevant risk factors. A literature search was performed including Cochrane, Medline, Pubmed, Pubmed Central, clinicaltrials.gov, and Embase from January 2018 to January 2025. This was performed using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Data was extracted and random effect models constructed using Review Manager (RevMan Version 7.2.0 The Cochrane Collaboration). Outcomes were reported as pooled hazard ratios (pHR) with 95% confidence intervals (95% CI). Clinically relevant subgroups were analyzed. A total of 6 studies comprising 3609 patients were selected for analysis. PARP inhibitors were beneficial regardless of patient age, Eastern Cooperative Oncology Group (ECOG) score, disease stage, timing of surgery, chemotherapy response, or high-risk classification. Patients with visible residual disease (VRD) after primary cytoreductive surgery (pCRS) derived significant benefit (pHR 0.61, 95% CI 0.48-0.77, p-value < 0.001). In contrast, no significant PFS benefit was observed for patients with VRD after interval cytoreductive surgery (iCRS) (pHR 0.63, 95% CI 0.36-1.09, p-value = 0.10). Although PARP inhibitors benefit various patient subgroups, our analysis did not demonstrate a PFS benefit in patients with VRD following iCRS. Residual disease status appears to be prognostically important for patients undergoing iCRS with maintenance PARP inhibitors. Further analyses of clinical risk factors stratified according to genetic subgroup is required. Prospero 2025 CRD420251007940, available at: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251007940.