Xu Yangchun, Ding Lei, Tian Yuan, Bi Miaomiao, Han Ning, Wang Ling
Department of Dermatology, The Second Hospital of Jilin University, Changchun, China.
Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, China.
Front Oncol. 2021 Feb 22;10:573801. doi: 10.3389/fonc.2020.573801. eCollection 2020.
This meta-analysis investigated the comparative efficacy and safety of PARP inhibitor monotherapy as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC). Electronic databases were systematically searched for relevant RCTs. The primary endpoint was PFS. The results were stratified based on three categories: BRCA mutated patients, HRD patients, and overall population. The secondary outcome were discontinuations due to adverse events and grade 3 or 4 adverse events in maintenance phase. Five eligible RCTs were included in the network meta-analysis. For patients with BRCA mutated ovarian cancer, olaparib-throughout (HR = 0.21 with 95% CrI: 0.081-0.55), rucaparib (HR = 0.23 with 95% CrI: 0.16-0.34), olaparib (HR = 0.27 with 95% CrI: 0.20-0.35), and niraparib (HR = 0.26 with 95% CrI: 0.17-0.41) were all highly effective in comparison with placebo at improving PFS. For HRD patients, both rucaparib (HR = 0.32 with 95% CrI: 0.24-0.42) and niraparib (HR = 0.38 with 95% CrI: 0.24-0.60) were all highly effective in comparison with placebo at improving PFS. For the overall population, olaparib-throughout (HR = 0.51 with 95% CrI: 0.34-0.76), rucaparib (HR = 0.37 with 95% CrI: 0.30-0.45), olaparib (HR = 0.35 with 95% CrI: 0.25-0.49), and niraparib (HR = 0.38 with 95% CrI: 0.30-0.48) were all highly effective in comparison with placebo at improving PFS. Regarding grade 3 or 4 adverse events, the incidence of grade 3 or 4 toxicity reactions to rucaparib and niraparib were significantly higher than in the olaparib group. In terms of discontinuations due to adverse events, the treatment discontinuations were not significantly different between the three drugs. In summary, all the included maintenance treatment regimens are effective regardless of BRCA mutational status, and no statistically significant differences between rucaparib, niraparib and Olaparib in terms of PFS. In terms of safety profile, the three drugs present manageable adverse events. Clinicians should consider potential adverse events related to each of these interventions in clinical practice, and the adverse events are generally manageable.
本荟萃分析研究了聚（ADP-核糖）聚合酶（PARP）抑制剂单药作为铂敏感复发性卵巢癌（ROC）维持治疗的相对疗效和安全性。系统检索电子数据库以查找相关随机对照试验（RCT）。主要终点为无进展生存期（PFS）。结果根据三类进行分层：BRCA突变患者、同源重组缺陷（HRD）患者和总体人群。次要结局为维持期因不良事件导致的停药情况以及3级或4级不良事件。五项符合条件的RCT纳入了网状荟萃分析。对于BRCA突变的卵巢癌患者，全程使用奥拉帕利（风险比[HR]=0.21，95%可信区间[CrI]：0.081 - 0.55）、芦卡帕利（HR = 0.23，95% CrI：0.16 - 0.34）、奥拉帕利（HR = 0.27，95% CrI：0.20 - 0.35）和尼拉帕利（HR = 0.26，95% CrI：0.17 - 0.41）与安慰剂相比，在改善PFS方面均非常有效。对于HRD患者，芦卡帕利（HR = 0.32，95% CrI：0.24 - 0.42）和尼拉帕利（HR = 0.38，95% CrI：0.24 - 0.60）与安慰剂相比，在改善PFS方面均非常有效。对于总体人群，全程使用奥拉帕利（HR = 0.51，95% CrI：0.34 - 0.76）、芦卡帕利（HR = 0.37，95% CrI：0.30 - 0.45）、奥拉帕利（HR = 0.35，95% CrI：0.25 - 0.49）和尼拉帕利（HR = 0.38，95% CrI：0.30 - 0.48）与安慰剂相比，在改善PFS方面均非常有效。关于3级或4级不良事件，芦卡帕利和尼拉帕利的3级或4级毒性反应发生率显著高于奥拉帕利组。在因不良事件导致的停药方面，三种药物之间的治疗停药情况无显著差异。总之，无论BRCA突变状态如何，所有纳入的维持治疗方案均有效，并且芦卡帕利、尼拉帕利和奥拉帕利在PFS方面无统计学显著差异。在安全性方面，这三种药物的不良事件均可管理。临床医生在临床实践中应考虑与这些干预措施相关的潜在不良事件，并且这些不良事件通常是可管理的。
