基于PARP抑制剂的新诊断晚期卵巢癌一线维持治疗在不同分子亚组中的应用：一项更新的系统评价和网络荟萃分析。
完整摘要 · 中文译文
背景：基于PARP抑制剂的维持治疗已成为新诊断晚期卵巢癌一线治疗的核心。随着治疗选择的扩展，治疗决策越来越依赖于BRCA突变和同源重组缺陷（HRD）状态。2026年NCCN指南强调生物标志物指导的维持治疗；然而，不同分子亚组间的比较证据仍然有限。我们进行了一项更新的网络荟萃分析，以比较基于PARP抑制剂的一线维持治疗策略的疗效和安全性。 方法：我们检索了主要数据库和会议论文，截至2026年4月1日，纳入评估新诊断晚期上皮性卵巢癌、输卵管癌或原发性腹膜癌一线维持治疗的随机对照试验。符合条件的干预措施包括PARP抑制剂单药治疗、PARP抑制剂联合抗血管生成治疗、抗血管生成单药治疗和安慰剂。主要分析关注BRCA突变人群和HRD阳性人群的无进展生存期（PFS）；次要和探索性分析涵盖意向治疗人群、HRD阳性非BRCA突变人群和同源重组正常人群。安全性结局包括≥3级不良事件和治疗中断。采用频率学派随机效应模型。 结果：纳入7项试验，共3，930例患者。与安慰剂相比，基于PARP抑制剂的维持治疗显著改善了PFS，在BRCA突变和HRD阳性人群中获益最强。PARP抑制剂单药治疗也显著改善了PFS，在 HRD阳性但非BRCA突变人群，支持HRD状态在BRCA突变之外的临床相关性。意向治疗人群中的获益小于生物标志物选择人群。同源重组修复正常人群中的获益证据不一致。间接比较显示，一种活性方案相较于另一种并无统计学显著优势。在连通网络内，在PARP抑制基础上加用抗血管生成治疗的PFS增量获益未得到统计学显著证实；该比较受限于联合治疗证据基础有限，以及由于网络断开而无法将PAOLA-1纳入主网络。无统计学显著证据表明一线贝伐珠单抗暴露会改变相对PFS获益。敏感性分析结果与主要分析一致。PARP抑制剂单药治疗与安慰剂相比增加了≥3级不良事件；联合治疗的安全性比较仍有限。 结论：本网络荟萃分析支持在晚期卵巢癌中采用以生物标志物为导向、以PARP抑制剂为基础的一线维持治疗，BRCA突变和HRD阳性人群的PFS获益最大。在连通网络内，没有任何活性方案显示出统计学显著优势。在PARP抑制基础上加用抗血管生成治疗的增量获益仍不确定，因为联合策略的连通网络证据有限，且PAOLA-1无法纳入主要网络。 主要网络。这些发现不应被解读为对奥拉帕利联合贝伐珠单抗或一般联合维持治疗策略临床价值的否定证据。治疗选择应综合分子状态、既往贝伐珠单抗暴露情况、安全性、治疗可及性和患者偏好。 系统评价注册：https://www.crd.york.ac.uk/PROSPERO/，标识符 CRD420261382266。
完整摘要 · 英文原文
BACKGROUND: PARP inhibitor-based maintenance has become central to first-line treatment of newly diagnosed advanced ovarian cancer. With expanding therapeutic options, treatment selection increasingly relies on BRCA mutation and homologous recombination deficiency (HRD) status. The 2026 NCCN Guidelines emphasize biomarker-directed maintenance; however, comparative evidence across molecular subgroups remains limited. We conducted an updated network meta-analysis to compare efficacy and safety of PARP inhibitor-based first-line maintenance strategies. METHODS: We searched major databases and conference proceedings to 1 April 2026 for randomized controlled trials evaluating first-line maintenance in newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. Eligible interventions included PARP inhibitor monotherapy, PARP inhibitor plus antiangiogenic therapy, antiangiogenic monotherapy, and placebo. Primary analyses focused on progression-free survival (PFS) in BRCA-mutated and HRD-positive populations; secondary and exploratory analyses covered intention-to-treat, HRD-positive non-BRCA-mutated, and homologous recombination proficient populations. Safety outcomes included grade ≥3 adverse events and treatment discontinuation. A frequentist random-effects model was applied. RESULTS: Seven trials involving 3,930 patients were included. PARP inhibitor-based maintenance significantly improved PFS versus placebo, with the strongest benefit in BRCA-mutated and HRD-positive populations. PARP inhibitor monotherapy also significantly improved PFS in the HRD-positive non-BRCA-mutated population, supporting clinical relevance of HRD status beyond BRCA mutation alone. Benefit in the intention-to-treat population was smaller than in biomarker-selected populations. Evidence of benefit in the homologous recombination proficient population was inconsistent. Indirect comparisons showed no statistically significant superiority of one active regimen over another. Within the connected network, no statistically significant incremental PFS benefit was established for adding antiangiogenic therapy to PARP inhibition; this comparison was limited by the restricted evidence base for combination therapy and the inability to incorporate PAOLA-1 into the primary network because of network disconnection. No statistically significant evidence indicated that frontline bevacizumab exposure modified the relative PFS benefit. Sensitivity analyses yielded results consistent with the primary analysis. PARP inhibitor monotherapy increased grade ≥3 adverse events versus placebo; comparative safety of combinations remained limited. CONCLUSIONS: This network meta-analysis supports biomarker-directed PARP inhibitor-based first-line maintenance in advanced ovarian cancer, with the greatest PFS benefit in BRCA-mutated and HRD-positive populations. No active regimen demonstrated statistically significant superiority within the connected network. The incremental benefit of adding antiangiogenic therapy to PARP inhibition remains uncertain because connected-network evidence for combination strategies was limited and PAOLA-1 could not be incorporated into the primary network. These findings should not be interpreted as evidence against the clinical value of olaparib plus bevacizumab or combination maintenance strategies in general. Treatment selection should integrate molecular status, prior bevacizumab exposure, safety, treatment availability, and patient preference. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261382266.