Cost-benefit of pre-treatment dihydropyrimidine dehydrogenase genotyping to individualise fluoropyrimidine-based chemotherapy in a contemporary Australian setting

Abstract

Background: Adverse events (AEs) due to fluoropyrimidine-based anticancer treatment are strongly influenced by interindividual variability in the enzyme dihydropyrimidine dehydrogenase (DPD). A major cause of DPD deficiency is the presence of certain variants of the encoding gene DPYD. International studies have found that pre-treatment DPYD genotype guided dose reductions is cost-effective in reducing severe AEs, however data in the Australian setting is limited.

The objective of this study is to assess the cost-benefit of pre-treatment DPYD genotyping for patients receiving fluoropyrimidines in an Australian clinical setting.

Methods: A cost-benefit model was developed to compare costs and number of grade 3–4 AEs for patients tested for the DPYD genotype versus a historical cohort. The proportion of patients with grade 3–4 AEs was informed by a DPYD trial conducted in Queensland. Costs of AEs were estimated using Australian Refined Diagnosis-Related Groups (AR-DRG) data. A cohort of 1000 patients was simulated. One-way sensitivity analyses were performed.

Results: The model estimated that there would be an additional 80 grade 3–4 AEs in the historical cohort compared to the DPYD cohort. This came at a cost of $85,294 equal to $1075 paid per AE avoided. The breakeven cost for the test is estimated to be $175/patient and there would be a cost saving of $85/patient if the cost of the test was $90. The sensitivity analyses showed that costs of gastrointestinal AEs were the main driver of the cost-benefit analysis with a break-even price of between $111 and $238. All the sensitivity analyses resulted in cost-savings if the cost of the test was $90.

Conclusion: DPYD testing is projected to help avoid 80 grade 3–4 AEs per 1000 patients treated with fluoropyrimidine-based anticancer therapy. DPYD genotyping is likely to result in costs saving if the cost of testing is less than $175 per patient.