Abstract
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.