Ji Shiya, Chen Lu, Yu Yebo, Chen Xupeng, Wei Liwen, Gou Lili, Shi Cheng, Zhuang Susu
Department of Health Education, Nanjing Municipal Center for Disease Control and Prevention, No.3, Zizhulin Road, Nanjing, Jiangsu Province, 210003, China.
Clinical Medicine College, Yangzhou University, Yangzhou, China.
J Ovarian Res. 2025 Jan 30;18(1):18. doi: 10.1186/s13048-025-01599-1.
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).
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.
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.
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.
聚（ADP - 核糖）聚合酶抑制剂（PARPis）已显示出对卵巢癌有良好的疗效。这项网络荟萃分析（PROSPERO注册号CRD42024503390）全面评估了PARPis在铂敏感复发性卵巢癌（PSROC）中的有效性和安全性。
从电子数据库中获取2024年1月6日前发表的文章。该研究评估并比较了生存结局，包括总生存期（OS）、无进展生存期（PFS）、第二次无进展生存期（PFS2）、首次后续治疗时间（TFST）、第二次后续治疗时间（TSST）和无化疗间期（CFI）。此外，还研究了安全性结局，特别关注3 - 4级治疗中出现的不良反应（TEAE）。还根据BRCA和HRD（同源重组缺陷）状态对OS和PFS进行了评估。
审查了六项随机对照试验，发现四种PARPis（奥拉帕利、尼拉帕利、鲁卡帕利和氟唑帕利）在总体人群以及HRD和BRCAm（BRCA突变）亚组中均显著提高了PFS。只有奥拉帕利在总体人群中与安慰剂相比显示出OS有显著改善（风险比[HR] 0.73；95%置信区间[CI] 0.60 - 0.90），在BRCAm亚组中也是如此。所有分析的PARPis在延长PFS2、TFST、TSST和CFI方面均有显著疗效。出于安全性考虑，PARPis可显著增加TEAE（3 - 4级）的发生率，而与其他PARPis相比，奥拉帕利的血液学TEAE（3 - 4级）事件最少。
所有纳入的PARPis在生存结局方面均显示出不同程度的益处，且安全性概况对PSROC患者是可接受的。其中奥拉帕利在疗效和安全性方面表现最佳。
