Abstract B001: Next-generation sequencing in ovarian cancer to identify actionable mutations

Abstract Objective PARP inhibitors have demonstrated significant benefit in ovarian cancers with evidence of homologous recombination deficiency. Next-generation sequencing (NGS) testing in ovarian cancer is not currently reimbursed across Canada and real-world data is lacking. The aim of this study was to identify actionable genomic alterations beyond somatic BRCA1/2 testing using tumor/plasma NGS testing (including genomic instability scoring (GIS)). Method: This is a retrospective single tertiary center (Jewish General Hospital, Montreal, Canada) study. Tissue somatic BRCA1/2 testing was performed through our local Molecular Pathology facility. NGS testing (including GIS) was performed using the Myriad Genetics MyChoice CDx and/or FoundationOne CDx testing. The GIS score for each assay enabled identification of tumors with homologous recombination deficiency (HRD). Results: Since 2019, 170 JGH HGSOC patients have had somatic BRCA1/2 testing with a mutation rate of 24.7%. Of those patients, 89 had NGS testing identifying 23.6% with pathogenic/likely pathogenic BRCA1/2 mutation and 13.5% with non-BRCA pathogenic/likely pathogenic HR mutations. Interestingly, 5/89 (5.6%) patients had non-HR actionable gene mutations. Furthermore, 64 of the 89 cases had HRD status reported showing 10 patients (15.6%) with positive HRD scores without pathogenic/likely pathogenic HR gene mutations. Six cases received inconclusive results and 17 were not reported (total of 23/89 cases: 25.8%). Together, these data reveal missed opportunities for PARP inhibitor therapy in 13.5% (non-BRCA HR mutations) and in 15.6% (HRD without HR gene mutations) representing a total of 29.1% of patients, as well as an additional potential cases from who did not have an HRD result reported (25.8%). Conclusion: Performing NGS testing with HRD scoring beyond BRCA1/2 testing increases the proportion of patients who would benefit from targeted therapy including PARP inhibitors from 24.7% to over 50%. Citation Format: Olivia Mckeeman, Angela Tatar, Shannon Salvador, Walter Gotlieb, Susie Lau, Melica Brodeur. Next-generation sequencing in ovarian cancer to identify actionable mutations [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr B001.