Aims: Fluoropyrimidine (FP) treatment can cause severe treatment-related adverse events in patients with reduced dihydropyrimidine dehydrogenase activity. Pre-treatment DPYD genotyping can identify patients who may benefit from dose reduction. Previous economic evaluations of DPYD testing-guided treatment were based on randomised controlled trial (RCT)-derived data and may not be applicable in routine clinical practice. This is the first study to evaluate the cost-utility of DPYD testing-guided pharmacogenomic (PGx) treatment of solid tumours using a real-world evidence (RWE)-data driven approach.
Methods: A semi-Markov model informed by RWE compared DPYD testing-guided treatment with standard care without testing. Patients transitioned between three health states: progression-free, progressed disease, and death. Costs and quality-adjusted life years (QALYs) were estimated over a 1-year time horizon. In Scenario 1, DPYD testing costs were applied to all FP-eligible patients, reflecting routine implementation of a pre-treatment testing strategy. In Scenario 2, testing costs were applied only to DPYD heterozygous patients, representing an alternative costing assumption commonly used in cost-based economic evaluations. Probabilistic sensitivity analyses (PSA) assessed uncertainty.
Results: In Scenario 1, DPYD testing-guided treatment was associated with an incremental cost of AU$212 and an incremental gain of 0.0014 QALYs, yielding an incremental cost-effectiveness ratio (ICER) of AU$154,360/QALY. This exceeded the willingness-to-pay threshold of AU$75,000/QALY, with a 0.4% probability of cost-effectiveness. In Scenario 2, the incremental cost decreased to AU$40 with an incremental QALY gain of 0.001, yielding an ICER of AU$29,440/QALY and a 100% probability of cost-effectiveness.
Conclusion: DPYD testing-guided FP treatment was unlikely to be cost-effective when evaluated as a population-wide testing strategy but appeared cost-effective under alternative cost-based testing assumptions commonly used in implementation-focused evaluations. These findings suggest that cost-effectiveness estimates are sensitive to testing pathway assumptions and highlight the value of real-world evidence in PGx economic evaluations to inform implementation decisions.