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Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：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人们的关注。回顾性研究显示，PARP抑制剂维持治疗进展后，铂类化疗的预后较差，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，并评估他们对治疗的反应。我们专注于化疗患者的无进展间期（PFI）≥6个月前铂类治疗后，基于BRCA状态。
方法：我们分析了北京大学肿瘤医院的真实数据，在2016年1月至2022年12月期间，上皮性卵巢癌进展为PARP抑制剂维持治疗后的后续治疗。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%)存在BRCA1/2野生型突变.使用的PARP抑制剂是Olaparib（n=62，60.8%），尼拉帕尼（n=35，34.3%），和其他（n=5，4.9%）。总有效率(ORR)为41.2%,至第二次进展的中位时间（mTTSP）为8.1个月（95CI5.8-10.2）。在PARP抑制剂维持治疗进展后的91名铂类敏感患者（PFI≥6个月），65名患者随后接受铂类药物治疗。其中,30例在PARP抑制剂维持治疗之前接受了一线化疗。根据BRCA状态对这30例患者进行的分析显示，ORR分别为16.7％和33.3％，mTTSP分别为7.1（95％CI4.9-9.1）和6.2个月（95％CI3.7-8.3，P=0.550），对于BRCA突变和野生型患者，分别。其余35例患者在PARP抑制剂维持治疗前接受过两行或更多行化疗，ORR分别为57.1%和42.9%，mTTSP分别为18.0（95％CI5.0-31.0）和8.0个月（95％CI4.9-11.1，P=0.199），对于BRCA突变和野生型患者，分别。
结论：不同BRCA状态患者的生存结局无差异。此外，对于在PARP抑制剂维持治疗之前接受过两行或更多行化疗的患者，没有发现PARP抑制剂对后续治疗的负面影响，不管BRCA的地位。
方法：我们分析了北京大学肿瘤医院的真实数据，在2016年1月至2022年12月期间，上皮性卵巢癌进展为PARP抑制剂维持治疗后的后续治疗。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%)存在BRCA1/2野生型突变.使用的PARP抑制剂是Olaparib（n=62，60.8%），尼拉帕尼（n=35，34.3%），和其他（n=5，4.9%）。总有效率(ORR)为41.2%,至第二次进展的中位时间（mTTSP）为8.1个月（95CI5.8-10.2）。在PARP抑制剂维持治疗进展后的91名铂类敏感患者（PFI≥6个月），65名患者随后接受铂类药物治疗。其中,30例在PARP抑制剂维持治疗之前接受了一线化疗。根据BRCA状态对这30例患者进行的分析显示，ORR分别为16.7％和33.3％，mTTSP分别为7.1（95％CI4.9-9.1）和6.2个月（95％CI3.7-8.3，P=0.550），对于BRCA突变和野生型患者，分别。其余35例患者在PARP抑制剂维持治疗前接受过两行或更多行化疗，ORR分别为57.1%和42.9%，mTTSP分别为18.0（95％CI5.0-31.0）和8.0个月（95％CI4.9-11.1，P=0.199），对于BRCA突变和野生型患者，分别。
结论：不同BRCA状态患者的生存结局无差异。此外，对于在PARP抑制剂维持治疗之前接受过两行或更多行化疗的患者，没有发现PARP抑制剂对后续治疗的负面影响，不管BRCA的地位。
