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

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 (w$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.