Sun Guojuan, Liu Yi
The Ward Section of Home Overseas Doctors, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Gynaecology and Obstetrics, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Front Pharmacol. 2024 Sep 18;15:1460285. doi: 10.3389/fphar.2024.1460285. eCollection 2024.
The landscape of poly (ADP-ribose) polymerase (PARP) inhibitor treatment for ovarian cancer (OC) is continually evolving. This research aimed to evaluate the efficacy and safety of PARP inhibitors compared to placebo as a maintenance therapy for OC patients.
We conducted a search of PubMed, Embase, Web of Science, and the Cochrane Library databases for randomized controlled trials (RCTs) involving the use of PARP inhibitors as maintenance therapy in OC patients, up to 16 June 2024. Data regarding progression-free survival (PFS), overall survival (OS), chemotherapy-free interval (CFI), time to first subsequent therapy or death (TFST), time to second subsequent therapy or death (TSST), and treatment-emergent adverse events (TEAEs) were aggregated. Pooled hazard ratio (HR) and their corresponding 95% confidence intervals (CI) were calculated for PFS, OS, CFI, TFST, and TSST. Additionally, the relative risk (RR) and 95% CI for TEAEs were determined.
This meta-analysis encompassed 20 RCTs involving 7,832 participants. The overall analysis demonstrated that maintenance therapy with PARP inhibitors led to significant improvements in PFS (HR: 0.398, 95% CI = 0.339-0.467, 95% PI = 0.219-0.724), OS (HR: 0.677, 95% CI = 0.582-0.788, 95% PI = 0.546-0.839), CFI (HR: 0.417, 95% CI = 0.368-0.472, 95% PI = 0.265-0.627), TFST (HR: 0.441, 95% CI = 0.391-0.498, 95% PI = 0.308-0.632), and TSST (HR: 0.574, 95% CI = 0.507-0.649, 95% PI = 0.488-0.674) compared with placebo. Subgroup analyses further indicated that PARP inhibitor maintenance treatment significantly improved PFS, regardless of homologous recombination status (all < 0.05). However, the risks of any grade (RR = 1.046, 95% CI = 1.032-1.059, 95% PI = 1.028-1.055) and grade ≥3 TEAEs (RR = 2.931, 95% CI = 2.641-3.253, 95% PI = 2.128-3.792) were increased by PARP inhibitor maintenance therapy compared to placebo.
Our research elucidated the benefits of maintenance therapy with PARP inhibitors in patients with OC, showing improvements in PFS, OS, CFI, TFST, and TSST. Vigilance regarding TEAEs is paramount for clinicians implementing PARP inhibitor maintenance therapy in clinical practice.
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024560286.
聚（ADP - 核糖）聚合酶（PARP）抑制剂治疗卵巢癌（OC）的格局在不断演变。本研究旨在评估PARP抑制剂与安慰剂相比作为OC患者维持治疗的疗效和安全性。
我们检索了PubMed、Embase、Web of Science和Cochrane图书馆数据库，以查找截至2024年6月16日涉及将PARP抑制剂用作OC患者维持治疗的随机对照试验（RCT）。汇总了无进展生存期（PFS）、总生存期（OS）、无化疗间期（CFI）、首次后续治疗或死亡时间（TFST）、第二次后续治疗或死亡时间（TSST）以及治疗中出现的不良事件（TEAE）的数据。计算了PFS、OS、CFI、TFST和TSST的合并风险比（HR）及其相应的95%置信区间（CI）。此外，还确定了TEAE的相对风险（RR）和95%CI。
这项荟萃分析纳入了20项RCT，涉及7832名参与者。总体分析表明，与安慰剂相比，PARP抑制剂维持治疗在PFS（HR：0.398，95%CI = 0.339 - 0.467，95%预测区间 = 0.219 - 0.724）、OS（HR：0.677，95%CI = 0.582 - 0.788，95%预测区间 = 0.546 - 0.839）、CFI（HR：0.417，95%CI = 0.368 - 0.472，95%预测区间 = 0.265 - 0.627）、TFST（HR：0.441，95%CI = 0.391 - 0.498，95%预测区间 = 0.308 - 0.632）和TSST（HR：0.574，95%CI = 0.507 - 0.649，95%预测区间 = 0.488 - 0.674）方面有显著改善。亚组分析进一步表明，无论同源重组状态如何，PARP抑制剂维持治疗均显著改善PFS（均P < 0.05）。然而，与安慰剂相比，PARP抑制剂维持治疗增加了任何级别（RR = 1.046，95%CI = 1.032 - 1.059，95%预测区间 = 1.028 - 1.055）和≥3级TEAE的风险（RR = 2.931，95%CI = 2.641 - 3.253，95%预测区间 = 2.128 - 3.792）。
我们的研究阐明了PARP抑制剂维持治疗对OC患者的益处，显示在PFS、OS、CFI、TFST和TSST方面有所改善。对于临床医生在临床实践中实施PARP抑制剂维持治疗而言，对TEAE保持警惕至关重要。
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