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PMID: 42038388 已发表 · epublish 英语

The effect of PARP inhibitor-based targeted therapy on BRCA-mutated ovarian cancer: systematic literature review.

Frontiers in oncology ·第 16 卷

Panjarwanto DA, Nabila P, Octavia L, Indrawan IWA, Utomo RP, Permana AY, Kaspan, Adnyana IGHE, Javier RM, Akbar MZH

摘要

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. This study aimed to systematically evaluate the efficacy and safety of PARP inhibitor-based therapy in patients with BRCA-mutated ovarian cancer. 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. 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. 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.

关键词
BRCA mutations PARP inhibitors ovarian cancer systematic review and meta-analysis targeted therapy
文献信息
期刊
Frontiers in oncology
期刊简称
Front Oncol
ISSN
2234-943X
语言
英语
国家/地区
Switzerland
NLM ID
101568867
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