Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) are the standard of care for first-line maintenance in advanced ovarian cancer, but their benefit varies by BRCA and homologous recombination deficiency (HRD) status, and no head-to-head comparisons are available. Methods: We conducted an indirect comparison of PARPi regimens using reconstructed individual patient data (IPD) from Kaplan–Meier curves of phase III randomized trials (SOLO1, PRIMA, PAOLA1, ATHENA, FLAMES). Progression-free survival (PFS) was the primary endpoint; overall survival (OS) was exploratory. Subgroups were defined as BRCA−mutated (BRCA+), BRCA−/HRD+, and BRCA−/HRD−. Safety outcomes were assessed through a network meta-analysis of adverse drug reactions (ADRs). Results: In BRCA+ patients, olaparib + bevacizumab achieved the largest PFS improvement (HR = 0.27; 95%CI: 0.19–0.39), followed by olaparib monotherapy, while niraparib performed significantly worse. In BRCA−/HRD+, olaparib + bevacizumab was superior to niraparib and rucaparib, with restricted mean survival time (RMST) gains of 3–4 months. In BRCA−/HRD−, PARPi produced only a modest benefit, with no advantage over bevacizumab monotherapy. Exploratory OS analysis confirmed long-term survival with olaparib in BRCA+ but not in the other subgroups. Safety analysis indicated olaparib had the most favorable hematological profile, while niraparib was associated with the highest rates of severe anemia, thrombocytopenia, and neutropenia, despite showing lower gastrointestinal toxicity and fatigue incidence. Conclusions: PARPi efficacy depends strongly on BRCA and HRD status. Olaparib-based regimens provide the greatest clinical benefit with acceptable safety in BRCA+ and HRD+ disease, whereas PARPi appear to be of limited value in HRD-negative ovarian cancer.
背景：聚腺苷二磷酸核糖聚合酶抑制剂（PARPi）是晚期卵巢癌一线维持治疗的标准方案，但其疗效因BRCA和同源重组缺陷（HRD）状态而异，且缺乏头对头比较研究。方法：我们利用III期随机试验（SOLO1、PRIMA、PAOLA1、ATHENA、FLAMES）的Kaplan-Meier曲线重建个体患者数据，对PARPi方案进行间接比较。主要终点为无进展生存期（PFS），总生存期（OS）为探索性终点。亚组定义为BRCA突变型（BRCA+）、BRCA-/HRD+型及BRCA-/HRD-型。通过药物不良反应网络荟萃分析评估安全性结果。结果：在BRCA+患者中，奥拉帕利联合贝伐珠单抗的PFS改善最显著（HR=0.27；95%CI：0.19-0.39），奥拉帕利单药次之，而尼拉帕利疗效显著较差。在BRCA-/HRD+亚组中，奥拉帕利联合贝伐珠单抗优于尼拉帕利和卢卡帕利，限制性平均生存时间增益达3-4个月。在BRCA-/HRD-亚组中，PARPi仅产生有限获益，且未优于贝伐珠单抗单药治疗。探索性OS分析证实奥拉帕利在BRCA+患者中具有长期生存获益，但在其他亚组中未观察到该优势。安全性分析显示奥拉帕利血液学毒性谱最优，而尼拉帕利虽胃肠道毒性和疲劳发生率较低，但严重贫血、血小板减少和中性粒细胞减少发生率最高。结论：PARPi疗效高度依赖BRCA和HRD状态。在BRCA+和HRD+患者中，基于奥拉帕利的方案能提供最大临床获益且安全性可接受，而在HRD阴性卵巢癌中PARPi的治疗价值有限。
肿瘤(癌症)患者之家