Abstract
INTRODUCTION: Ovarian cancer remains one of the leading causes of gynecologic cancer mortality worldwide, largely due to late-stage diagnosis and high recurrence rates. Mutations in the BRCA1 and BRCA2 genes disrupt homologous recombination repair pathways, creating a therapeutic vulnerability that can be exploited by poly (ADP-ribose) polymerase (PARP) inhibitors. Although PARP inhibitors have demonstrated clinical benefits in BRCA-mutated ovarian cancer, variability across clinical studies has led to uncertainty regarding their overall effectiveness and long-term outcomes. OBJECTIVES: This study aimed to systematically evaluate the efficacy and safety of PARP inhibitor-based therapy in patients with BRCA-mutated ovarian cancer. METHODS: A systematic literature review and meta-analysis were conducted following PRISMA 2020 guidelines. Four electronic databases (PubMed, Scopus, EMBASE, and Cochrane Library) were searched for studies published between 2013 and 2025. Eligible studies included randomized controlled trials and observational cohort studies evaluating PARP inhibitors in patients with BRCA-mutated ovarian cancer. Risk of bias was assessed using the Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a meta-analytic approach. RESULTS: Twelve studies met the inclusion criteria for qualitative synthesis, including five randomized controlled trials and seven observational cohort studies. Four studies were eligible for quantitative meta-analysis. PARP inhibitor therapy significantly improved progression-free survival (PFS) (HR: 0.62, 95% CI: 0.56-0.68). In contrast, improvement in overall survival (OS) was modest (HR: 0.82, 95% CI: 0.68-0.98) and less consistently reported. Hematologic toxicities, particularly anemia and thrombocytopenia, were the most frequently reported grade ≥3 adverse events. CONCLUSION: PARP inhibitors provide a significant progression-free survival benefit in patients with BRCA-mutated ovarian cancer, particularly when used as maintenance therapy. However, the impact on overall survival remains uncertain, highlighting the need for longer follow-up and further prospective studies to optimize treatment strategies and clarify long-term clinical outcomes.