Clinical validation of different HRD assays in high-grade serous ovarian cancer in Greek population.

Abstract

e17591 Background: Homologous recombination deficiency (HRD) - encompassing presence of BRCA1/2 mutations and/or genomic instability (GIS) - is an established predictive and prognostic biomarker in patients with high-grade serous ovarian cancer (HGSC). HRD was initially assessed in registrational clinical trials with Myriad MyChoice CDx and Foundation ONE tests. We have previously shown the concordance between the results of three commercially available in Greece HRD assays (Myriad MyChoice CDx, AmoyDx HRD Focus Panel, OncoScan). However, no clinical validation for the application of these assays in clinical practice in the Greek population currently exists. Methods: We retrospectively evaluated 206 patients with HGSC that received treatment in the Oncology Department of Alexandra University Hospital between 01/2019 and 08/2024. All patients underwent HRD testing with either Myriad myChoice NGS panel CDx or AmoyDx HRD Focus NGS Panel/ OncoScan as part of the nationwide patient support program from the Hellenic Society of Medical Oncology (HeSMO). Results: Median age at diagnosis was 61.5 years (SD ±11.5). 193 patients were diagnosed with FIGO stage III/IV ovarian cancer. Most patients underwent primary debulking surgery (PDS) (122; 59.2%) while 67 patients (30.5%) underwent interval debulking surgery (IDS). Debulking was optimal in 153 (74.6%) patients. 92 patients (44.7%) were tested for HRD with Myriad MyChoice assay while 114 patients (55.3%) were tested for AmoyDx or OncoScan. There was concordance between the two methods as shown in Table 1 (p= 0.174 ) Median PFS time was 13.3 months for the HRD- group, 23.4 months for the HRD+/BRCAwt and 39.3 months for the HRD+/BRCAmut group tested with Myriad myChoice CDx assay. Median PFS was 14.6 months for the HRD-, 33.6 months for the HRD+/BRCAwt and non-estimable for the HRD+/BRCAmut subgroup tested with the AmoyDx HRD Focus Panel. There were statistically significant differences in PFS among the different subgroups (χ 2 = 22.039, p= 0.001) however the trend was the same for both HRD assays. Conclusions: Overall, PFS trends were similar regardless of the HRD assay applied. The performance of both methods (Myriad MyChoice CDx and AmoyDx HRD Focus Panel) is comparable in the real-world setting. HRD and BRCA mutation results according to the method used. Myriad MyChoice AmoyDx p -value HRD- 37 (40.2) 44 (38.6) 0.174* HRD + /BRCA - 25 (27.2) 47 (41.2) HRD + /BRCA+ 24 (26.1) 23 (20.20) Inconclusive/Insufficient 6 (6.5) 0 (0.0) * p -value for chi-square test ( χ 2 = 3.497).