The Real-World Impact of PARP Inhibitor Maintenance Therapy in High Grade Serous Tubo-Ovarian and Peritoneal Cancers

TL;DR

This study compares the effectiveness of different PARP inhibitors in treating high-grade serous cancers, finding that olaparib benefits BRCA2-mutated patients more than BRCA1-mutated ones.

Contribution

The study provides real-world evidence comparing PARP inhibitors in high-grade serous cancers, revealing differential benefits based on BRCA mutation status.

Findings

Olaparib provides significantly better progression-free survival in BRCA2-mutated patients compared to BRCA1-mutated patients.

Niraparib and rucaparib show similar clinical benefits in the recurrent cancer setting.

Primary maintenance with niraparib in BRCA wild-type patients shows a median progression-free survival of 11 months.

Abstract

PARP inhibitor (olaparib, niraparib, or rucaparib) maintenance treatment is a standard treatment option in patients with high-grade serous tubo-ovarian and peritoneal cancers following surgery and chemotherapy. Whether olaparib, niraparib, or rucaparib have similar clinical benefit is an area of clinical investigation. The real-world data evaluation of olaparib, niraparib, and rucaparib maintenance can provide valuable insight that can aid clinical decision-making. We conducted a retrospective observational study at our centre to evaluate survival outcomes and compare clinical trial data. We observed significantly better survival benefit from olaparib in BRCA2 germline mutated patients compared to BRCA1 mutated patients. In the recurrent setting, niraparib and rucaparib provide similar clinical benefits.

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.

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