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2022-RA-567-ESGO The Geneva HRD test: clinical validation on 469 samples from the PAOLA-1 trial
  1. Yann Christinat1,
  2. Liza Ho1,
  3. Sophie Clément2,
  4. Catherine Genestie3,
  5. Jalid Sehouli4,
  6. Antonio Gonzalez Martin5,
  7. Ursula Denison6,
  8. Keiichi Fujiwara7,
  9. Ignace Vergote8,
  10. Germana Tognon9,
  11. Sakari Hietanen10,
  12. Eric Pujade-Lauraine11,
  13. Isabelle Ray-Coquard12 and
  14. Thomas A McKee1
  1. 1Clinical Pathology Division, Geneva University Hospitals, Genève, Switzerland
  2. 2Université de Genève, Geneva, Switzerland
  3. 3Gustave Roussy, Paris, France
  4. 4Charité – Universitätsmedizin Berlin (CVK), Berlin, Germany
  5. 5MD Anderson Cancer Center Madrid, Madrid, Spain
  6. 6Klinik Hietzing, Institute for gynaecological oncology und senology, Vienna, Austria
  7. 7Saitama Medical University International Medical Center, Saitama, Japan
  8. 8University hospitals leuven and Leuven Cancer Institute, Leuven, Belgium
  9. 9Spedali Civili di Brescia, Brescia, Italy
  10. 10Turku University Hospital, Department of Obstetrics and Gynecology, Turku, Finland
  11. 11ARCAGY-GINECO, Paris, France
  12. 12Centre Leon Bérard, Lyon, France


Introduction/Background The efficacy of the Myriad myChoice® Homologous Recombination Deficiency (HRD) test to guide use of PARP inhibitors has been demonstrated in several phase III trials. However, its high failure rate and limited accessibility establish a need for a clinically validated laboratory developed test.

Methodology As part of the ENGOT HRD European Initiative, a subset of the PAOLA-1/ENGOT-ov25 phase 3 trial was analyzed in the Geneva University Hospitals with the OncoScan™ CNV Assay and an in-house algorithm developed using TCGA data. Results were compared to Myriad myChoice Genomic Instability Score (GIS) with respect to the progression-free survival in the Olaparib+Bev and placebo+Bev arms.

Results The analysis of the TCGA cohort revealed that a normalization of the number of LST (large-scale state transitions) by the number of whole-genome doubling events allows a better separation and classification of HRD samples than the Myriad GIS. On the 469 PAOLA-1 samples, the Geneva test yielded a lower failure rate than Myriad (10/469 vs 59/469 inconclusive results) and positive and negative agreement values of 96% (204/213) and, respectively, 81% (159/197). In Geneva HRD-positive samples, the hazard ratio (HR) was 0.40 (95% CI: 0.28–0.57; figure 1). For Myriad, the HR was 0.35. In BRCA wild-type and Geneva HRD-positive samples, the HR was 0.53 (Myriad: 0.41). Of note, in this subpopulation the Geneva test and the Myriad test yielded a similar 1-year PFS (87% and 88%) but a different 2-year PFS (52% vs 60%).

Abstract 2022-RA-567-ESGO Figure 1

Conclusion The proposed test is a viable alternative to the Myriad myChoice HRD test and can easily be implemented in a clinical laboratory for routine practice. The performance of the tests is similar in terms of hazard ratio but the lower failure rate of the Geneva HRD test allows a 10% increase in the number of patients receiving a conclusive laboratory result.

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