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.