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. 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.