806 Assessment of the RAD51 test to determine homologous recombination deficiency (HRD) in patients with newly diagnosed advanced high-grade epithelial ovarian cancer carcinoma (HGOC)

Introduction/Background HRD identifies HGOC patients most likely to benefit from PARPi. Unlike commercially available genomic-scar HRD tests(CT), functional testing by RAD51, has potential to provide real-time readout of current HR status and may be more reliable to detect HRD. Methodology This single-institution study aims to assess immunofluorescence-based RAD51 foci test to correlate it with CT's results and treatment outcomes in newly diagnosed advanced HGOC patients. Tumors with <10%RAD51+ tumor cells in S/G2-phase were classified as HRD positive(HRD+). HRD status agreement rate between CT and RAD51 tests was calculated. Median progression-free survival(mPFS) was estimated in each subgroup. Results Between 2020–2023, 59 patients had CT and RAD51 tests performed on archived tumour samples. Both tests were carried out on forty-six patients' tumor samples. All patients received platinum-chemotherapy as 1st-line therapy. As maintenance, 46% received PARPi and 20% Bevacizumab alone. 54.3%(25/46) and 41.3%(19/46) tumors were classified as HRD+ according to CT and RAD51 respectively. 12 and 7 patients were identified as HRD+ only by an assay, CT and RAD51 respectively. Concordance-rate between both tests was 58.7%(95%CI,43.3–72.7). Based on CT, mPFS of HRD+ and HRD negative(HRD-) patients was 17.4m and 11.1m(HR0.54; 95%CI,0.24–1.8) respectively. mPFS for HRD and HRD- patients based on RAD51 was 16.4m and 14.1m(HR0.78; 95%CI,0.35–1.74) respectively. Among patients with concordant test results, mPFS was 19.4m and 11m for HRD+ and HRD- patients, respectively. Among patients with no-concordant test results, mPFS was 17.4m and 16.1m for patients defined as HRD+ only by CT and RAD51 tests. Conclusion Our preliminary data showed both tests can identify HRD+ and HRD- subpopulations showing comparable outcomes. However, data seems to show low correlation-rate between both tests. RAD51 test has identified among patients with HRD- by CT, a subset of HRD+ having better mPFS . Our data suggest that combination of genomic and functional HRD tests might improve molecular diagnostic accuracy of HGOC. Disclosures There are no conflicts of interest in relation to this publication.