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Upfront Dpyd Genotype-Guided Treatment for Fluoropyrimidine-Based Chemotherapy in Advanced and Metastatic Colorectal Cancer: A Cost-Effectiveness Analysis Publisher Pubmed



Fariman SA1 ; Jahangard Rafsanjani Z2 ; Hasanzad M3, 4 ; Niksalehi K1 ; Nikfar S1
Authors
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Authors Affiliations
  1. 1. Department of Pharmacoeconomics and Pharmaceutical administration, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Medical Genomics Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Value in Health Regional Issues Published:2023


Abstract

Objectives: Fluoropyrimidines are the most widely used chemotherapy drugs for advanced and metastatic colorectal cancer (CRC). Individuals with certain DPYD gene variants are exposed to an increased risk of severe fluoropyrimidine-related toxicities. This study aimed to evaluate the cost-effectiveness of preemptive DPYD genotyping to guide fluoropyrimidine therapy in patients with advanced or metastatic CRC. Methods: Overall survival of DPYD wild-type patients who received a standard dose and variant carriers treated with a reduced dose were analyzed by parametric survival models. A decision tree and a partitioned survival analysis model with a lifetime horizon were designed, taking the Iranian healthcare perspective. Input parameters were extracted from the literature or expert opinion. To address parameter uncertainty, scenario and sensitivity analyses were also performed. Results: Compared with no screening, the genotype-guided treatment strategy was cost-saving ($41.7). Nevertheless, due to a possible reduction in the survival of patients receiving reduced-dose regimens, it was associated with fewer quality-adjusted life-years (9.45 vs 9.28). In sensitivity analyses, the prevalence of DPYD variants had the most significant impact on the incremental cost-effectiveness ratio. The genotyping strategy would remain cost-saving, as long as the genotyping cost is < $49 per test. In a scenario in which we assumed equal efficacy for the 2 strategies, genotyping was the dominant strategy, associated with less costs (∼$1) and more quality-adjusted life-years (0.1292). Conclusions: DPYD genotyping to guide fluoropyrimidine treatment in patients with advanced or metastatic CRC is cost-saving from the perspective of the Iranian health system. © 2023 International Society for Health Economics and Outcomes Research
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