# Real-world outcomes following PARP inhibitor maintenance in ovarian cancer by BRCA status: a retrospective cohort study

## TL;DR

This study finds that using PARP inhibitors as first-line treatment for ovarian cancer may reduce the effectiveness of future chemotherapy, regardless of BRCA status.

## Contribution

The study provides real-world evidence on the impact of first-line PARP inhibitor use on subsequent treatment outcomes in ovarian cancer.

## Key findings

- Subsequent treatment responses are shorter after first-line PARPi in ovarian cancer.
- Shortened responses occur in both second- to third- and third- to fourth-line treatments.
- Shortened effects of subsequent treatment occur irrespective of BRCA status.

## Abstract

The introduction of poly (adenosine-diphosphate ribose) polymerase inhibitors (PARPis) has significantly improved progression-free survival for patients with ovarian cancer after response to first-line platinum-based chemotherapy. Yet, there are concerns that PARPi may compromise response to further platinum due to cross-resistance mechanisms. This study investigates the clinical effectiveness of chemotherapy post-progression on PARPi maintenance therapy after initial platinum-based treatment for ovarian cancer, regardless of BRCA mutations, using real-world data. Additionally, this study summarises results across randomised trials of PARPi as first-line maintenance.

This study used a United States-based electronic health record-derived de-identified database. A retrospective descriptive analysis was conducted on patients with ovarian cancer diagnosed from 1 January 2015 onwards. Patient data were collected, including BRCA and homologous recombination deficiency (HRD) status. Time to next treatment (TTNT), treatment-free interval (TFI), and the impact of BRCA and HRD status were assessed.

Among 3649 patients, 81% had known BRCA status, of whom 83% were BRCA-negative, 17% were BRCA-positive, and 19% had unknown BRCA status. The majority (80%) had unknown HRD status. Notably, 17% received first-line PARPi. Patients with BRCA mutations displayed longer TTNT and TFI when receiving first-line PARPi initially. However, after receiving subsequent treatments, BRCA-mutated and non-mutated patients demonstrated shorter TFI and TTNT intervals, suggesting a possible influence of PARPis on subsequent chemotherapy efficacy.

The study underscores previous concerns that initiating PARPi in the first line may impact treatment duration and intervals for subsequent therapies in patients with ovarian cancer. Future investigations should explore the interplay of PARPi maintenance in the first-line setting, HRD status, and response to subsequent platinum-based therapies.

•Subsequent treatment responses are shorter after first-line PARPi in ovarian cancer.•Shortened responses occur in both second- to third- and third- to fourth-line treatments.•Shortened effects of subsequent treatment occur irrespective of BRCA status.•Later effects of first-line PARPi by HRD status are unclear due to small numbers.

Subsequent treatment responses are shorter after first-line PARPi in ovarian cancer.

Shortened responses occur in both second- to third- and third- to fourth-line treatments.

Shortened effects of subsequent treatment occur irrespective of BRCA status.

Later effects of first-line PARPi by HRD status are unclear due to small numbers.