Homologous recombination deficiency should be tested for in patients with advanced stage high-grade serous ovarian cancer aged 70 years and over

Objective. Due to limited data on homologous recombination deficiency (HRD) in older patients (>= 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group. Methods. From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice (R) CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx (R). HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS >= 33 & >= 42 analyzed). Results. Of 1140 participants, 21% were >= 70 years. In total, 26% ( n = 298) had a BRCA1/2 PV and HRD, 29% ( n = 329) were HRD/ BRCA wild-type, 33% ( n = 372) non-HRD, and 12% HR-status unknown ( n = 141). HRD rates were higher in younger participants, 59% ( n = 476/802), compared to 40% ( n = 78/197) of older participants (GIS >= 42) [ p < 0.001]; similar rates demonstrated with GIS >= 33, 66% vs 48% [ p < 0.001]. g BRCA PVs observed in 24% younger vs 8% of older participants ( p < 0.001); s BRCA in 8% vs 10% ( p = 0.2559), and HRD (GIS >= 42) not due to g BRCA was 35% vs 31% ( p = 0.36). Conclusions. HRD frequency was similar in participants aged < 70 and >= 70 years (35% vs 31%) when the contribution of g BRCA was excluded; rates of s BRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).