Biomarker results from the KGOG3056/NIRVANA-R trial: Maintenance niraparib plus bevacizumab in patients with platinum-sensitive, recurrent ovarian cancer previously treated with a PARP inhibitor.

5556 Background: While poly(ADP-ribose) polymerase inhibitors (PARPi) have demonstrated clinical success in prolonging progression-free survival (PFS) in ovarian cancer, the efficacy of subsequent chemotherapy following progression from PARPi maintenance is markedly decreased. Modest PFS benefits with PARPi rechallenge following a response to platinum-based chemotherapy has been reported, but the efficacy of PARPi rechallenge with bevacizumab remains unknown. Methods: NIRVANA-R, a phase 2 study, evaluated niraparib rechallenge with bevacizumab in patients with platinum-sensitive recurrent ovarian cancer previously treated with PARPi. Eligibility required a response to the most recent platinum regimen. The primary endpoint was 6-month progression-free rate. Biomarker exploration included the analysis of BRCA status, homologous recombination deficiency (HRD) status, circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs) using whole-exome sequencing, as well as CA-125 levels. Results: Between 2019 and 2023, 44 patients were enrolled; over 65% had received≧3 lines of chemotherapy. The estimated 6-month progression-free rate was 68% [95% confidence interval (CI) 55–85%]. Key prognostic factors included treatment-free interval after penultimate platinum-based chemotherapy (TFI P ) (TFI P ≥24 months vs. TFI P <24 months; 82% vs. 56%), achieving a complete response (CR) [CR vs. partial response; 86% vs. 57%] or normal CA-125 levels (0–35 vs. >35 U/mL; 72% vs. 25%) in response to the most recent chemotherapy. Median PFS was 11·5 months [95% CI 7.9-not reached (NR)]. Ongoing biomarker analysis includes BRCA status, HRD status, ctDNA and CTCs, and these results will be updated in subsequent reports. No new safety signals were identified with niraparib rechallenge plus bevacizumab. Conclusions: Niraparib rechallenge with bevacizumab showed promising efficacy, particularly in patients with TFI P ≥24 months, CR, or normal CA-125 levels following previous chemotherapy, supporting further clinical research. Ongoing exploration of HRD, ctDNA, CTCs, and other biomarkers will provide further insights into treatment stratification and outcomes. Clinical trial information: NCT04734665 . Estimated 6-month progression-free rate according to prognostic factors. Factors N 6 month PFS rate (95% CI) p-value 1. Response to most recent chemotherapy CR 17 85% (69-100%) 0.148 PR 27 57% (40-82%) 2. platinum-free interval from penultimate chemotherapy <24 months 24 56% (38-83%) 0.018 ≥24 months 20 82% (65-100%) 3. BRCA status BRCA wild-type 16 56% (35-90%) 0.806 BRCA mutation 22 73% (55-96%) unknown 6 80% (52-100%) 4. Progression during/after previous PARPi therapy Progression during previous PARPi 30 68% (52-89%) 0.846 Progression after previous PARPi 14 68% (50-100%)