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Ovarian cancer
2022-RA-1310-ESGO Cost-effectiveness of unselected multigene germline and somatic genetic testing for epithelial ovarian cancer
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  1. Li Sun1,
  2. Monika Sobocan2,3,4,
  3. Isabel V Rodriguez5,
  4. Xia Wei1,2,
  5. Ashwin Kalra2,3,
  6. Samuel Oxley2,3,
  7. Michail Sideris2,3,
  8. Robert D Morgan6,
  9. Dhivya Chandrasekaran2,
  10. Kelly Rust7,
  11. Pavlina Spiliopoulou7,
  12. Rowan E Miller8,
  13. Shanthini M Crusz8,
  14. Michelle Lockley9,
  15. Naveena Singh10,
  16. Asma Faruqi10,
  17. Laura Casey10,
  18. Elly Brockbank3,
  19. Saurabh Phadnis2,3,
  20. Tina Mills-Baldock11,
  21. Fatima El-Khouly11,
  22. Lucy A Jenkins12,
  23. Andrew Wallace13,
  24. Munaza Ahmed12,
  25. Ajith Kumar12,
  26. Elizabeth M Swisher5,
  27. Charlie Gourley7,
  28. Barbara M Norquist5,
  29. D Gareth Evans13,
  30. Rosa Legood1 and
  31. Ranjit Manchanda1,2,3,14,15
  1. 1Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK
  2. 2Wolfson Institute for Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
  3. 3Department of Gynaecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK
  4. 4Division for Gynaecology and Perinatology, University Medical Centre Maribor, Maribor, Slovenia
  5. 5Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA
  6. 6Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
  7. 7Institute of Genetics and Cancer, Cancer Research UK Edinburgh Centre, University of Edinburgh, Edinburgh, UK
  8. 8Department of Medical Oncology, Barts Health NHS Trust, London, UK
  9. 9Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, UK
  10. 10Department of Pathology, Barts Health NHS Trust, London, UK
  11. 11Department of Medical Oncology, Barking, Havering and Redbridge University Hospitals, Essex, UK
  12. 12North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK
  13. 13Manchester Centre for Genomic Medicine, Division of Evolution, infection and Genomic Sciences, University of Manchester, Manchester, UK
  14. 14Institute of Clinical Trials and Methodology, Faculty of Population Health Sciences, University College London, London, UK
  15. 15Department of Gynaecology, All India Institute of Medical Sciences, New Delhi, India

Abstract

Introduction/Background Parallel panel-germline and somatic-testing in all women with ovarian-cancer (OC) identifies more pathogenic-variants (PV) benefitting from poly-ADP-ribose (PARP) inhibitor (PARP-i) therapy, and unaffected PV-relatives for precision prevention. This study aims to estimate cost-effectiveness and population impact of parallel panel-germline and somatic BRCA-testing all OC-patients incorporating PARP-i therapy, compared with family-history (FH)/clinical-criteria based germline BRCA-testing in UK and USA health-systems.

Methodology Microsimulation cost-effectiveness modelling using data from 2,391 unselected population-based OC-patients recruited to UK (n=1,483) and USA (n=908) research studies. The lifetime costs-&-effects of BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline-testing and somatic BRCA1/BRCA2-testing in all OC-cases (BRCA-mutated patients undergo PARP-i therapy) (Strategy-A), was compared with FH/clinical-criteria based germline BRCA-testing (Strategy-B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade-testing undergo relevant OC and breast-cancer (BC) risk-reduction interventions (risk-reducing salpingo-oophorectomy, MRI/mammography, chemoprevention or risk-reducing-mastectomy). We also evaluated cost-effectiveness of germline-panel testing alone (without PARP-i therapy). A lifetime horizon with payer/societal perspectives, along-with probabilistic and one-way sensitivity-analyses are presented. Incremental-cost-effectiveness-ratio (ICER): incremental-cost per quality-adjusted-life-year (QALY) gained, was compared to £30,000/QALY(UK) and $100,000/QALY(USA) thresholds. OC-incidence, BC-incidence and prevented deaths were estimated.

Results Compared with clinical-criteria/FH-based BRCA-testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline-testing and BRCA1/BRCA2 somatic-testing all OC patients incorporating PARP-i therapy demonstrates UK-ICERs (payer-perspective=£42,433/QALY; societal-perspective=£41,622/QALY) and USA-ICERs (payer-perspective=$145,071/QALY; societal-perspective=$144,564/QALY) are higher than UK/NICE and USA cost-effectiveness thresholds. Strategy-A becomes cost-effective if PARP-i costs fall by 32% (UK) or 33% (USA), or overall-survival (OS) with PARP-i reaches HR=0.28. Unselected panel-germline testing (without PARP-i therapy) is extremely cost-effective from payer-perspective (UK-ICER=£11,291/QALY; USA-ICER=$68,808/QALY); and societal-perspectives (UK-ICER=£6,923/QALY; USA-ICER=$65,786/QALY). One year’s unselected testing could prevent 199 BC/OC-cases and 236 deaths in UK-women; and 523 BC/OC-cases and 581 deaths in USA-women.

Conclusion Unselected panel-germline and somatic BRCA-testing is currently not cost-effective but becomes cost-effective if PARP-i costs fall by 32%-33% or OS reaches HR=0.28. Regarding germline-testing, unselected panel-germline testing is highly cost-effective and should replace BRCA-testing alone.

https://doi.org/10.1136/ijgc-2022-ESGO.685

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