Department of Woman's and Child Health and Public Health Sciences, Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy.
Epidemiology and Biostatistics Facility, G-STeP Generator, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Eur J Cancer. 2023 Jul;187:77-86. doi: 10.1016/j.ejca.2023.03.035. Epub 2023 Apr 5.
In patients with newly diagnosed advanced high-grade serous and endometrioid epithelial ovarian cancer (EOC) first-line maintenance therapy with poly(ADP-ribose) polymerase inhibitors (PARPi) tremendously improved progression-free survival (PFS). Yet, data on the effect of PARPi in proportion to postoperative residual disease status were lacking.
A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items of Systematic reviews and Meta-Analysis (PRISMA) guidelines. We searched Medline/Pubmed, Embase and Cochrane databases as well as meeting abstracts until 18th March 2023. Hazard ratios (HRs) alongside their 95% confidence intervals (CIs) for PFS were extracted from the studies. A subgroup analysis was conducted to examine the effect of PARPi according to postoperative residual disease.
A total of six phase III randomised controlled trials were included and comprised SOLO 1, PAOLA 1, PRIMA, PRIME, ATHENA-MONO and VELIA. Patients who received PARPi following complete gross resection showed greatest PFS benefit. Compared with placebo, maintenance with PARPi significantly improved PFS in patients with macroscopic residual disease (pooled HR 0.55; 95% CI 0.44-0.68). This magnitude was comparable to that found in patients with complete gross resection (pooled HR 0.53; 95% CI 0.41-0.67).
Patients with macroscopic residual disease benefit from PARPi at the same extent as cases with complete gross resection. However, patients with complete gross resection who were treated with PARPi show the most favourable PFS rates. Hence, the pursuit of achieving complete cytoreduction remains valid in the PARPi era.
在新诊断的高级别浆液性和子宫内膜样上皮性卵巢癌（EOC）患者中，聚（ADP-核糖）聚合酶抑制剂（PARPi）的一线维持治疗极大地改善了无进展生存期（PFS）。然而，缺乏关于 PARPi 对术后残留疾病状态的影响的数据。
根据系统评价和荟萃分析的首选报告项目（PRISMA）指南进行了系统评价和荟萃分析。我们检索了 Medline/Pubmed、Embase 和 Cochrane 数据库以及会议摘要，直到 2023 年 3 月 18 日。从研究中提取 PFS 的风险比（HR）及其 95%置信区间（CI）。进行了亚组分析，以检查根据术后残留疾病的 PARPi 效应。
共纳入六项 III 期随机对照试验，包括 SOLO 1、PAOLA 1、PRIMA、PRIME、ATHENA-MONO 和 VELIA。接受完全大体切除后接受 PARPi 治疗的患者 PFS 获益最大。与安慰剂相比，PARPi 维持治疗显著改善了有宏观残留疾病的患者的 PFS（汇总 HR 0.55；95%CI 0.44-0.68）。这一程度与完全大体切除的患者相当（汇总 HR 0.53；95%CI 0.41-0.67）。
有宏观残留疾病的患者从 PARPi 中获益的程度与完全大体切除的患者相同。然而，接受 PARPi 治疗且完全大体切除的患者显示出最有利的 PFS 率。因此，在 PARPi 时代，追求实现完全细胞减灭仍然是有效的。
