Gynecology Department, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Ministry of Education of People's Republic of China, Beijing, 100142, China.
J Ovarian Res. 2024 Mar 5;17(1):55. doi: 10.1186/s13048-024-01381-9.
BACKGROUND: The efficacy of subsequent therapy after poly-ADP-ribose polymerase (PARP) inhibitor maintenance treatment has raised concerns. Retrospective studies show worse outcomes for platinum-based chemotherapy after progression of PARP inhibitor-maintenance therapy, especially in BRCA-mutant patients. We aimed to describe subsequent therapy in ovarian cancer patients after PARP inhibitor-maintenance therapy and evaluate their response to treatment. We focused on chemotherapy for patients with a progression-free interval (PFI) of ≥ 6 months after prior platinum treatment, based on BRCA status. METHODS: We analyzed real-world data from Peking University Cancer Hospital, subsequent therapy after progression to PARP inhibitor-maintenance therapy for epithelial ovarian cancer between January 2016 and December 2022. Clinicopathological characteristics and treatment outcomes were extracted from medical records. The last follow-up was in May 2023. RESULTS: A total of 102 patients were included, of which 29 (28.4%) had a germline BRCA1/2 mutation and 73 (71.6%) exhibited BRCA1/2 wild-type mutations. The PARP inhibitors used were Olaparib (n = 62, 60.8%), Niraparib (n = 35, 34.3%), and others (n = 5, 4.9%). The overall response rate (ORR) was 41.2%, and the median time to second progression (mTTSP) was 8.1 months (95%CI 5.8-10.2). Of 91 platinum-sensitive patients (PFI ≥ 6 months) after progression to PARP inhibitor-maintenance therapy, 65 patients subsequently received platinum regimens. Among them, 30 had received one line of chemotherapy before PARP inhibitor-maintenance therapy. Analysis of these 30 patients by BRCA status showed an ORR of 16.7% versus 33.3% and mTTSP of 7.1 (95% CI 4.9-9.1) versus 6.2 months (95% CI 3.7-8.3, P = 0.550), for BRCA-mutant and wild-type patients, respectively. For the remaining 35 patients who had received two or more lines of chemotherapy before PARP inhibitor-maintenance therapy, ORR was 57.1% versus 42.9%, and mTTSP was 18.0 (95% CI 5.0-31.0) versus 8.0 months (95% CI 4.9-11.1, P = 0.199), for BRCA-mutant and wild-type patients, respectively. CONCLUSION: No differences in survival outcomes were observed among patients with different BRCA statuses. Furthermore, for patients who had undergone two or more lines of chemotherapy before PARP inhibitor maintenance therapy, no negative effects of PARP inhibitors on subsequent treatment were found, regardless of BRCA status.
背景：多聚 ADP 核糖聚合酶（PARP）抑制剂维持治疗后后续治疗的疗效引起了关注。回顾性研究表明，PARP 抑制剂维持治疗后进展的患者进行铂类化疗的结局较差，尤其是 BRCA 突变患者。我们旨在描述 PARP 抑制剂维持治疗后卵巢癌患者的后续治疗，并评估其治疗反应。我们根据 BRCA 状态，重点关注铂类治疗后无进展间隔（PFI）≥6 个月的患者的化疗。
方法：我们分析了 2016 年 1 月至 2022 年 12 月北京大学肿瘤医院上皮性卵巢癌患者接受 PARP 抑制剂维持治疗后进展的真实世界数据。从病历中提取临床病理特征和治疗结果。最后一次随访是在 2023 年 5 月。
结果：共纳入 102 例患者，其中 29 例（28.4%）存在种系 BRCA1/2 突变，73 例（71.6%）表现为 BRCA1/2 野生型突变。使用的 PARP 抑制剂分别为奥拉帕利（n=62，60.8%）、尼拉帕利（n=35，34.3%）和其他（n=5，4.9%）。总缓解率（ORR）为 41.2%，第二次进展的中位时间（mTTSP）为 8.1 个月（95%CI 5.8-10.2）。在进展至 PARP 抑制剂维持治疗后 PFI≥6 个月的 91 例铂类敏感患者中，65 例患者随后接受了铂类方案。其中，30 例患者在接受 PARP 抑制剂维持治疗前接受了一线化疗。对这 30 例患者按 BRCA 状态进行分析，BRCA 突变和野生型患者的 ORR 分别为 16.7%和 33.3%，mTTSP 分别为 7.1（95%CI 4.9-9.1）和 6.2 个月（95%CI 3.7-8.3，P=0.550）。对于另外 35 例在接受 PARP 抑制剂维持治疗前接受了两线或更多线化疗的患者，BRCA 突变和野生型患者的 ORR 分别为 57.1%和 42.9%，mTTSP 分别为 18.0（95%CI 5.0-31.0）和 8.0 个月（95%CI 4.9-11.1，P=0.199）。
结论：不同 BRCA 状态的患者在生存结果方面无差异。此外，对于在接受 PARP 抑制剂维持治疗前接受了两线或更多线化疗的患者，无论 BRCA 状态如何，均未发现 PARP 抑制剂对后续治疗有负面影响。
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