Zhang Depu, Li Shuo, Zhang Xinxin, Peng Jingwei, Zhang Shiqian
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China.
Department of Gynecology Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Front Oncol. 2022 Aug 18;12:955124. doi: 10.3389/fonc.2022.955124. eCollection 2022.
This study assessed the real-world application, effectiveness, and safety of olaparib and niraparib as maintenance therapies in patients with platinum-sensitive recurrent ovarian cancer (PSROC) in China and investigated clinical factors associated with prolonged benefits of poly ADP-ribose polymerase (PARP) inhibitors to help guide clinician treatment-decision making in daily practice.
This real-world single-center retrospective cohort study was conducted at the Shandong Cancer Hospital and Institute. Archival data of consecutive patients diagnosed with PSROC who achieved a complete response (CR) or partial response (PR) after the last platinum-based chemotherapy and treated with olaparib or niraparib as maintenance therapy from August 2018 to September 2021 were collected.
Overall, 106 women were included in the cohort. Seventy-two (68%) patients were treated with olaparib, while 34 (32%) received niraparib; 99.1% of the patients were diagnosed with high-grade serous carcinoma, and 73.6% had FIGO stages III-IV. Approximately 71.7% of the patients had received PARP inhibitors after the second platinum-based line and 44.3% of the patients achieved a CR in their last platinum-based therapy. The median platinum-free interval (PFI) after the penultimate platinum-based therapy was 10 (95% CI: 10-13.6) months. The median PFS was 21 (95% CI: 13-24.5) months and the median CFI was 22 (95% CI: 16-26.5) months. Consistent with the univariate analysis, the multivariate analysis identified three independent factors associated with prolonged progression-free survival (PFS) and chemotherapy-free interval (CFI): breast cancer susceptibility gene (BRCA) mutant type (p = 0.005 and p = 0.003); PFI ≥12 months (p = 0.01 and p = 0.006); and CR to last platinum-based therapy (p = 0.016 and p = 0.019). It was found that there was no appreciable difference in any grade 3-4 hematological AE between patients who received olaparib and niraparib.
Maintenance treatment with olaparib and niraparib is effective and well tolerated for PSROC patients in real-world clinical practice. Three clinical factors were identified that predicted prolonged survival under maintenance therapy with PARP inhibitors: BRCA mutant type, PFI ≥12 months, and CR to last platinum-based therapy. These findings should be further confirmed with an appropriately powered analysis in studies with larger sample sizes.
本研究评估了奥拉帕利和尼拉帕利在中国铂敏感复发性卵巢癌（PSROC）患者中作为维持治疗的实际应用情况、有效性及安全性，并调查了与聚ADP-核糖聚合酶（PARP）抑制剂延长获益相关的临床因素，以帮助指导临床医生在日常实践中的治疗决策。
本项真实世界单中心回顾性队列研究在山东省肿瘤医院暨山东省肿瘤防治研究院开展。收集了2018年8月至2021年9月期间连续诊断为PSROC且在上次铂类化疗后达到完全缓解（CR）或部分缓解（PR）并接受奥拉帕利或尼拉帕利作为维持治疗的患者的存档数据。
总体而言，该队列纳入了106名女性。72名（68%）患者接受了奥拉帕利治疗，34名（32%）接受了尼拉帕利治疗；99.1%的患者被诊断为高级别浆液性癌，73.6%为国际妇产科联盟（FIGO）Ⅲ-Ⅳ期。约71.7%的患者在二线铂类治疗后接受了PARP抑制剂治疗，44.3%的患者在上次铂类治疗中达到CR。倒数第二次铂类治疗后的中位无铂间期（PFI）为10（95%CI：10-13.6）个月。中位无进展生存期（PFS）为21（95%CI：13-24.5）个月，中位化疗间期（CFI）为22（95%CI：16-26.5）个月。与单因素分析一致，多因素分析确定了与无进展生存期（PFS）延长和无化疗间期（CFI）相关的三个独立因素：乳腺癌易感基因（BRCA）突变类型（p=0.005和p=0.003）；PFI≥12个月（p=0.分01和p=0.006）；以及对上次铂类治疗的CR（p=0.016和p=0.019）。结果发现，接受奥拉帕利和尼拉帕利治疗的患者在任何≥3-4级血液学不良事件方面均无明显差异。
在真实世界临床实践中，奥拉帕利和尼拉帕利作为维持治疗对PSROC患者有效且耐受性良好。确定了三个临床因素可预测PARP抑制剂维持治疗下的生存期延长：BRCA突变类型、PFI≥12个月以及对上次铂类治疗的CR。这些发现应在样本量更大的研究中通过适当的效能分析进一步证实。
