Efficacy and safety of PARP inhibitors in prostate cancer: An umbrella review of systematic reviews and meta-analyses

Prostate cancer is a significant cause of cancer-related deaths in men. Poly (ADP-ribose) polymerase inhibitors (PARPi) have been shown to improve progression-free survival, especially in patients with BRCA1/2 mutations and deficiencies in homologous recombination repair (HRR). We conducted systematic reviews and meta-analyses and found that PARPi, combined with androgen receptor inhibitors, significantly improved overall survival (OS) and progression-free survival (PFS) in BRCA1/2-mutant and HRR-deficient patients. PARPi therapies increased the incidence of adverse events (AEs), including fatigue, nausea, anemia, neutropenia, and thrombocytopenia. Among different PARP inhibitors, Olaparib, Talazoparib, and Rucaparib demonstrated the strongest efficacy in improving OS and PFS but were also linked to higher rates of AEs. Combination therapies with PARPi and hormonal treatments proved more effective than monotherapy, especially in genetically targeted subgroups like BRCA1/2-mutant patients. This umbrella review demonstrates that PARPi treatment significantly improves clinical outcomes, particularly in BRCA1/2-mutant and HRR-deficient mCRPC patients.