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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)
  1. Carmen Garcia-Duran1,
  2. Heura Domenech2,
  3. Guillermo Villacampa3,
  4. Juan Francisco Grau-Bejar2,
  5. Alba Llop-Guevara2,
  6. David Garcia-Illescas2,
  7. Roberta Mazzeo4,
  8. Sara Simonetti2,
  9. Lorena Fariñas-Madrid5,
  10. Lucia Musacchio6,
  11. Violeta Serra2 and
  12. Ana Oaknin7
  1. 1Gynecological Cancer Programme, Barcelona, Spain
  2. 2Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
  3. 3Hospital Universitari Val d’Hebron, Barcelona, Spain
  4. 4Vall d’Hebron Institute of Oncology (VHIO), Udine, Italy
  5. 5University of Udine, Barcelona, Spain
  6. 6Vall d’Hebron Institute of Oncology (VHIO), Rome, Italy
  7. 7Fondazione Policlinico Universitario A. Gemelli IRCCS, Barcelona, Spain

Abstract

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.

Abstract 806 Table 1

Agreement date between commercial genomic and RAD51 tests

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