Modeled economic and clinical impact of a multi-cancer early detection (MCED) test in a population with hereditary cancer syndromes

BackgroundIndividuals with hereditary cancer syndromes face elevated cancer risks. MCED tests may reduce late detection of cancer, which is associated with poorer survival and higher treatment costs. MCED has been projected to be cost-effective in its intended use population of adults 50 years or older who are at typical average-risk for cancer. This modeling study explores key economic and health outcomes of MCED testing in adults with hereditary cancer syndromes in the US.MethodsA state transition model compared annual MCED plus standard of care (SoC) screening with SoC alone for individuals aged 50 to 79 without prior cancer history, with any of 17 gene mutations - including BRCA1/2, ATM, PALB2, CHEK2, PTEN, and those associated with Lynch syndrome - without risk-reducing surgery. Nineteen solid cancer groupings were modeled; costs, life-years, and quality adjusted life-years (QALYs) were estimated over an individual’s lifetime discounted at 3% annually. Incidence rate ratios (IRRs) for first cancer incidence versus the general population were calculated based on lifetime risk of each cancer type for each gene mutation from literature. IRRs were weighted by the global prevalence of each mutation to determine an overall IRR per cancer type for the population. SEER-Medicare linked data informed resource use and costs, while the performance of the MCED test was based on Klein et al (2021).ResultsIn patients with hereditary cancer syndromes, MCED was projected to reduce initial incidence of cancers diagnosed in stage 3 or 4 by 42%. This led to a projected 17% reduction in cancer mortality in the population, primarily due to a 56% reduction in stage 4 mortality. At a price of $949 per test, annual MCED testing approached cost-neutrality in this high-risk population, with an incremental cost-effectiveness ratio of $1,966/QALY.ConclusionsAddition of MCED testing to SoC may improve outcomes in individuals with hereditary cancer syndromes while being near cost-neutral for this high-risk population.Legal entity responsible for the studyGrail Llc.FundingGrail Llc.DisclosureS. Raoof: Financial Interests, Personal, Advisory Role: Grail. A. Tafazzoli, A. Kansal: Financial Interests, Personal, Full or part-time Employment: Grail; Financial Interests, Institutional, Sponsor/Funding: Grail. A. Shaul, W. Ye: Financial Interests, Personal, Other, At the time of writing, employed by Evidera; Evidera received funding from Grail Llc. to conduct the study and develop this abstract. M. Fendrick: Financial Interests, Personal, Advisory Role: Grail.