Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer

Authors:
Ranjit Manchanda Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, Faculty of Population Health Sciences, University College London, London, UK
Department of Gynecology, All India Institute of Medical Sciences, New Delhi, India

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Li Sun Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK

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Monika Sobocan Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK
Division of Gynecology and Perinatology, University Medical Centre Maribor, Maribor, Slovenia

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Isabel V. Rodriguez Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA

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Xia Wei Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK

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Ashwin Kalra Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

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Samuel Oxley Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

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Michail Sideris Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

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Caitlin T. Fierheller Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

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Robert D. Morgan Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK

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Dhivya Chandrasekaran Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK

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Kelly Rust Institute of Genetics and Cancer, Cancer Research UK Edinburgh Centre, University of Edinburgh, Scotland, UK

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Pavlina Spiliopoulou School of Cancer Sciences, University of Glasgow, Scotland, UK

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Rowan E. Miller Department of Medical Oncology, Barts Health NHS Trust, London, UK

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Shanthini M. Crusz Department of Medical Oncology, Barts Health NHS Trust, London, UK

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Michelle Lockley Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, UK

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Naveena Singh Department of Pathology, Barts Health NHS Trust, London, UK

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Asma Faruqi Department of Pathology, Barts Health NHS Trust, London, UK

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Laura Casey Department of Pathology, Barts Health NHS Trust, London, UK

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Elly Brockbank Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

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Saurabh Phadnis Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Gynecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK

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Tina Mills-Baldock Department of Medical Oncology, Barking, Havering, and Redbridge University Hospitals, Essex, UK

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Fatima El-Khouly Department of Medical Oncology, Barking, Havering, and Redbridge University Hospitals, Essex, UK

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Lucy A. Jenkins North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK

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Andrew Wallace Manchester Centre for Genomic Medicine, Division of Evolution, Infection, and Genomic Sciences, University of Manchester, Manchester, UK

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Munaza Ahmed North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK

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Ajith Kumar North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK

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Elizabeth M. Swisher Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA

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Charlie Gourley Institute of Genetics and Cancer, Cancer Research UK Edinburgh Centre, University of Edinburgh, Scotland, UK

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Barbara M. Norquist Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA

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D. Gareth Evans Manchester Centre for Genomic Medicine, Division of Evolution, Infection, and Genomic Sciences, University of Manchester, Manchester, UK

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Rosa Legood Wolfson Institute of Population Health, CRUK Barts Cancer Centre, Queen Mary University of London, London, UK
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK

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Background: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)–based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. Methods: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) 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 of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year’s testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. Conclusions: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

Submitted September 30, 2022; final revision received November 25, 2023; accepted for publication December 18, 2023. Published online April 18, 2024.

These authors contributed equally to this study.

Author contributions: Concept and design: Manchanda, Legood. Model development: Manchanda, Sun, Legood. Patient management: Manchanda, Rodriguez, Kumar, Morgan, Chandrasekaran, Miller, Crusz, Singh, Faruqi, Casey, Brockbank, Phadnis, El-Khouly, Ahmed, Swisher, Gourley, Norquist, Evans. Genetic testing: Jenkins, Wallace. Data acquisition: Manchanda, Sobocan, Rodriguez, Morgan, Chandrasekaran, Rust, Spiliopoulou, Miller, Mills-Baldock, Swisher, Gourley, Norquist, Evans. Statistical/Data analysis: Manchanda, Sun, Legood. Data interpretation: All authors. Funding acquisition: Manchanda. Project administration: Manchanda, Sun, Sobocan, Wei, Kalra, Oxley, Sideris, Chandrasekaran, Lockley, Mills-Baldock. Supervision: Manchanda, Legood. Writing—original draft: Manchanda, Sun, Wei, Legood. Critical revision of the manuscript for important intellectual content and final approval: All authors.

Disclosures: Dr. Manchanda has disclosed receiving honoraria from the Israel National Institute for Health Policy Research, AstraZeneca, MSD, GSK, and EGL Genetics; receiving research support from GSK; serving as an advisory board member for GSK, Everything Genetic Ltd, and AstraZeneca; serving on a speakers’ bureau for GSK; and serving as a consultant for GSK and Everything Genetic Ltd. Dr. Miller has disclosed serving on an advisory board for GSK; and serving on a speaker’s bureau for GSK, AstraZeneca, and Merck & Co., Inc. Dr. Gourley has disclosed receiving research support from AstraZeneca, MSD, and GSK; and serving as a scientific advisor for AstraZeneca. Dr. Evans has disclosed receiving grant/research support from the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007). The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This study was funded by the Barts Charity (ECMG1B6R; R. Manchanda) and the Rosetrees Trust (R. Manchanda). Dr. Norquist has disclosed receiving grant/research support from the Department of Defense (DOD) funding grant OC180282.

Supplementary material: Supplementary material associated with this article is available online at https://doi.org/10.6004/jnccn.2023.7331. The supplementary material has been supplied by the author(s) and appears in its originally submitted form. It has not been edited or vetted by JNCCN. All contents and opinions are solely those of the author. Any comments or questions related to the supplementary materials should be directed to the corresponding author.

Correspondence: Ranjit Manchanda, PhD, Wolfson Institute of Population Health, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Email: r.manchanda@qmul.ac.uk

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