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201 Homologous recombination deficiency testing in advanced ovarian cancer: description of the ENGOT HRD European initiative
  1. E Pujade-Lauraine1,
  2. Y Christinat2,
  3. M D’incalci3,
  4. P Schouten4,
  5. A Buisson5,
  6. LC Heukamp6,
  7. T Van Gorp7,
  8. C Kramer8,
  9. T Mckee2,
  10. S Marchini9,
  11. E Hahnen10,
  12. P Saintigny11,
  13. E Ioana Braicu12,
  14. IB Vergote7,
  15. E Yaniz-Galende13 and
  16. I Ray-Coquard14
  2. 2Geneva University Hospitals, Diagnostic Department, Division of Pathology, Geneva, Switzerland
  3. 3Hospital, Humanitas University Campus, Building C, Humanitas Research , Pieve Emanuele (MI) , Italy
  4. 4Netherlands Cancer Institute, Department of Molecular Pathology, Amsterdam, Netherlands
  5. 5Centre Léon Bérard, Department of Biopathology, lyon, France
  6. 6Institute for Hämatopathologie Hamburg, Hamburg, Germany
  7. 7University Hospitals Leuven, Division of Gynaecological Oncology, Leuven, Belgium
  8. 8Leiden University Medical Center, Department of Pathology, Leiden, Netherlands
  9. 9Hospital, Humanitas University Campus, Building C, Laboratory of Cancer Pharmacology, Pieve Emanuele (MI), Italy
  10. 10University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
  11. 1111Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Department of Medical Oncology, lyon, France
  12. 12Universitätsmedizin Berlin, Department of Gynecology, with Center for Oncological Surgery, Berlin , Germany
  13. 13Institut Gustave Roussy et INSERMU981, Villejuif, France
  14. 14Centre Léon Bérard, Laboratoire RESHAPE U1290, lyon, France


Introduction/Background*Recently 3 Phase III first-line studies, PAOLA-1/ENGOT-ov25 (Ray-Coquard et al. NEJM 2019). PRIMA/ENGOT-ov26/GOG-3012 (Gonzales Martin et al. NEJM 2019) and VELIA/GOG-3005 (Coleman et al. NEJM 2019) have demonstrated that the addition of a PARP inhibitor (PARPi) to platinum-based therapy+/-bevacizumab improved progression-free survival (PFS) in advanced ovarian cancer (AOC) patients. The benefit was greater when the tumor was homologous recombination deficient (HRD) according to Myriad myChoice test, independently of BRCA status. The PAOLA-1 olaparib+bevacizumab maintenance regimen was approved in USA/Europe/Japan for HRD positive patients. The European initiative aims at evaluating various HRD tests on PAOLA-1 tumor samples to identify new reliable and feasible HRD tests

Methodology The HRD initiative has 2 components; one based on artificial intelligence with various partners and the other, the European HRD ENGOT initiative (EHEI), is led by academic research laboratories (RL) from ENGOT groups. The HRD test evaluation protocol for the EHEI RL includes 3 phases. The phase 1 (2019/12) brought together European RL. Because non-BRCA Homologous Recombination Repair (HRR) mutations have not been found predictive of PARPi activity in PAOLA-1 (Pujade-Lauraine et al, SGO 2021)) RL tests based on these mutations were not selected for the next phases. Phase 2 evaluated the correlation between RL tests and the Myriad myChoice test on tumor samples from 85 PAOLA-1 BRCA wild type patients using the KAPPA statistics. Phase 3 is the final PFS evaluation on more than 350 additional patient samples.

Result(s)*A total of 20 RL from 21 ENGOT groups participated to the EHEI phase 1. Half of them had a test mainly based on an HRR gene panel. Three RL did not pursue for various reasons (capacity, financial or regulatory). The remaining 7 RL from 6 countries (table 1) completed the phase 2 in May 2021 and may proceed to phase 3.

Abstract 201 Table 1

The 7 research laboratories which completed the phase 2 ENGOT European HRD initiatives

Conclusion*The EHEI is a unique collaboration of European academic laboratories involved in gynecologic oncology translational research with the aim of providing a reliable biomarker (HRD) for selecting AOC patients who could benefit most from PARPi+/-bevacizumab in first-line therapy. HRD tests performance will be described after their phase 3 is completed.

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