Background: Pivotal clinical trials have led to the routine clinical use of PARP inhibitor (PARPi) (olaparib, niraparib, or rucaparib) maintenance therapy in high-grade serous tubo-ovarian and peritoneal cancers. Whether various PARPis have comparable clinical impact in the real-world is an area of ongoing investigation. Methods: We conducted a retrospective study of all patients who received PARPi maintenance therapy at Nottingham Cancer Centre from October 2017 to April 2025. Clinical data were extracted from multidisciplinary team electronic health records, including age, BRCA mutation status, HRD status, treatment history, type of PARP inhibitor received, progression-free survival (PFS), and overall survival (OS). Results: A total of 177 patients had received PARPi therapy with a mean age of 63 years at diagnosis. In all, 94/177 (53.1%) had received PARPi as primary maintenance, while 83/177 (46.9%) were treated in the recurrent setting. All together, 25/177 (14.1%) had BRCA1 germline mutation and 21/177 (11.9%) had BRCA2 germline mutation. In the primary olaparib setting, PFS was significantly better in BRCA2 germline-mutated patients compared to BRCA1 germline-mutated patients [median PFS was not reached vs. 29.0 months, respectively,p= 0.002]. In BRCA, wild-type patients receiving primary niraparib, median PFS was 11 months. Median PFS for patients with upfront surgery was 37 months compared to 19 months in the interval debulking group but not significant (p= 0.49). In the recurrent setting, there was no significant difference in median PFS between niraparib and rucaparib [10 months vs. 9 months,p= 0.594]. Conclusions: BRCA2 germline-mutated patients obtained significantly greater benefit from olaparib compared to BRCA1-mutated patients. PFS benefit from niraparib (primary or recurrent setting) is comparable to clinical trials. There was no difference in benefit between niraparib and rucaparib in the recurrent setting.
背景：关键临床试验已使PARP抑制剂（奥拉帕利、尼拉帕利或鲁卡帕利）维持治疗成为高级别浆液性输卵管卵巢癌和腹膜癌的常规临床疗法。不同PARP抑制剂在真实世界中的临床效果是否具有可比性，仍是当前研究领域。方法：我们对2017年10月至2025年4月期间在诺丁汉癌症中心接受PARP抑制剂维持治疗的所有患者进行了回顾性研究。临床数据来源于多学科团队电子健康记录，包括年龄、BRCA突变状态、HRD状态、治疗史、PARP抑制剂类型、无进展生存期（PFS）和总生存期（OS）。结果：共177例患者接受PARP抑制剂治疗，诊断时平均年龄63岁。其中94/177例（53.1%）接受一线维持治疗，83/177例（46.9%）为复发后治疗。总体而言，25/177例（14.1%）携带BRCA1胚系突变，21/177例（11.9%）携带BRCA2胚系突变。在一线奥拉帕利治疗中，BRCA2胚系突变患者的PFS显著优于BRCA1胚系突变患者（中位PFS未达到 vs. 29.0个月，p=0.002）。在接受一线尼拉帕利治疗的BRCA野生型患者中，中位PFS为11个月。初始手术患者的中位PFS为37个月，而间歇性肿瘤细胞减灭术组为19个月，但差异不显著（p=0.49）。在复发治疗中，尼拉帕利与鲁卡帕利的中位PFS无显著差异（10个月 vs. 9个月，p=0.594）。结论：与BRCA1突变患者相比，BRCA2胚系突变患者从奥拉帕利治疗中获益显著更优。尼拉帕利（一线或复发治疗）的PFS获益与临床试验结果相当。在复发治疗中，尼拉帕利与鲁卡帕利的疗效无差异。
肿瘤(癌症)患者之家