779P - Assessment of the RAD51 test to determine homologous recombination deficiency (HRD) in patients (pts) with newly diagnosed advanced high-grade epithelial ovarian cancer carcinoma (HGOC)

Background

HRD is used to identify HGOC patients most likely to benefit from PARPi. Unlike commercially available genomic scar HRD tests (CT), functional testing by RAD51, have potential to provide a real-time readout of actual HR status and may be more reliable to detect HRD.

Methods

This single-institution study assesses the immunofluorescence-based RAD51 foci test and correlates it to CT and treatment outcomes in newly diagnosed advanced HGOC pts between 2020-2023. Tumors with <10% RAD51+ tumor cells in S/G2-phase were classified as HRD positive (HRD+). HRD status agreement rate between CT and RAD51 was calculated. Median progression-free survival (mPFS) was estimated in each subgroup.

Results

Overall, 53 pts had CT and RAD51 tests performed on archival tumour samples. Both tests were contributive for 38 pts. As 1st line therapy, all pts received platinum chemotherapy. As maintenance, 47% received PARPi and 18% Bevacizumab alone. % of HRD+ according CT and RAD51 was 55.3% (21/38) and 42.1% (16/38), respectively. Concordance rate between both tests was 50% (95%CI 34.8-65.2), with 12 and 7 pts identified as HRD+ only by CT and RAD51. Table: 779P

Based on CT, mPFS of HRD+ and HRP pts was 19.4m and 16.1m, respectively (HR 0.69; 95%CI, 0.26-1.85). Based on RAD51, mPFS for HRD and HRP pts was 19.4m and 14.3m (HR 0.70; 95%CI, 0.25-1.93), respectively. Among pts with consistent HRD test results, mPFS was 19.4 m and 11 m for HRD and HRP pts, respectively. Among disparate results, mPFS was 17.4m and 16.1m for pts defined as HRD only by CT and RAD51, respectively.

Conclusions

Our preliminary data showed both tests identified HRD and HRP subpopulations with similar outcomes despite low correlation between them. Among pts with HRP by CT, RAD51 identified a subset of HRD+ with better mPFS. Combination of genomic and functional HRD tests could improve molecular diagnostic accuracy of HGOC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

VHIO.

Disclosure

C. Garcia Duran: Financial Interests, Principal Investigator: AstraZeneca; Financial Interests, Speaker’s Bureau: GSK. G. Villacampa Javierre: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabrer, GSK; Financial Interests, Personal, Invited Speaker, Internal discussion about the interpretation of some published results: Pfizer; Financial Interests, Personal, Other, Collaborations with specific projects: Reveal Genomics. L. Fariñas Madrid: Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Speaker’s Bureau: GSK. D.G. Illescas: Financial Interests, Invited Speaker: GSK. V. Serra Elizalde: Financial Interests, Research Grant: Novartis. A. Llop-Guevara: Financial Interests, Research Grant: PharmaMar. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche, Seagen, OneXerna Therapeutics, Inc., Regeneron, Sutro Biopharma; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Amgen, AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Aprea Therapeutics AB, Regeneron Pharmaceuticals, Clovis Oncology Inc., EISAI limited Ltd., F. Hoffmann-La Roche Ltd., Immunogen Inc., Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc., PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019 . Scientific Track Member Gynaecological Cancers ESMO 2018 , ESMO 2020 , ESMO 2022 . Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines: ESMO; Non-Financial Interests, Leadership Role, ESMO GYN Co-Chair 2023-2025: ESMO; Non-Financial Interests, Leadership Role, Chair de Cervix Committee. 2022-2024: GCIG; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. All other authors have declared no conflicts of interest.