Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade serous or endometrioid ovarian cancer: A multi-national observational study

Maintenance therapy with a poly(ADP-ribose) polymerase-1/2 inhibitor (PARPi) improves survival outcomes in women with high-grade serous or endometroid ovarian cancer (HGS/EOC) whose disease responds to platinum-taxane chemotherapy, with the greatest benefit reported in BRCA-mutant/Homologous Recombination Deficient (HRD)-tumours. We report the prevalence of BRCA-mutant/HRD-tumours in women with newly diagnosed FIGO stage III/IV HGS/EOC in England, Wales and Northern Ireland between April 2021 and April 2022. These data represent the first year that routine HRD testing was available through the NHS. Eligibility criteria included newly diagnosed FIGO stage III/IV HGS/EOC. The Myriad myChoice® HRD assay was used to detect pathogenic BRCA1/2 variants and a genomic instability score (GIS) in formalin-fixed paraffin-embedded tumour tissue. Testing was performed during standard-of-care first-line therapy pathways. All patients gave informed consent for tumour testing. No cases were included that were tested as part of a clinical trial. Testing was co-ordinated by the NHS Genomic Hub Laboratory network. Tumour BRCA1/2 and GIS testing was requested for 2,829 patients. 2,474 (87.5%) and 2,178 (77.0%) patients were successfully tested for BRCA1/2 or GIS, respectively. 385 (15.6%) BRCA1/2 pathogenic variants were detected (BRCA1=220; BRCA2=165). The GIS was ≥42 in 814 (37.4%) patients. 510 (23.4%) patients had tumour BRCA1/2 wild-type and a GIS ≥42. GIS had a bimodal distribution, with BRCA1/2-mutant tumours having higher scores than wild-type tumours. In this study of women with newly diagnosed FIGO stage III/IV HGS/EOC, 895 (36.2%) were found to have a BRCA1/2 mutation and/or a GIS ≥42, and therefore had the opportunity to benefit from first-line PARPi maintenance therapy. This is the largest real-world evidence cohort for the prevalence of HRD-tumours in HGS/EOC. These data highlight the importance of HRD testing to optimise outcomes for eligible women. The rapid uptake of HRD testing in England, Wales and Northern Ireland also demonstrates the power of centralised NHS funding, centre specialisation and the Genomic Hub Laboratory network.