Background: Fluoropyrimidine therapy including capecitabine or 5-fluorouracil can result in severe treatment-related toxicity in up to 30% of patients. Toxicity is often related to reduced activity of dihydropyrimidine dehydrogenase, the main metabolic fluoropyrimidine enzyme, primarily caused by genetic DPYD polymorphisms. In a large prospective study, it was concluded that upfront DPYD-guided dose individualisation is able to improve safety of fluoropyrimidine-based therapy. In our current analysis, we evaluated whether this strategy is cost saving. Methods: A cost-minimisation analysis from a health-care payer perspective was performed as part of the prospective clinical trial (NCT02324452) in which patients prior to start of fluoropyrimidine-based therapy were screened for the DPYD variants DPYD*2A, c.2846A>T, c.1679T>G and c.1236G>A and received an initial dose reduction of 25% (c.2846A>T, c.1236G>A) or 50% (DPYD*2A, c.1679T>G). Data on treatment, toxicity, hospitalisation and other toxicity-related interventions were collected. The model compared prospective screening for these DPYD variants with no DPYD screening. One-way and probabilistic sensitivity analyses were also performed. Results: Expected total costs of the screening strategy were €2599 per patient compared with €2650 for non-screening, resulting in a net cost saving of €51 per patient. Results of the probabilistic sensitivity and one-way sensitivity analysis demonstrated that the screening strategy was very likely to be cost saving or worst case cost-neutral. Conclusions: Upfront DPYD-guided dose individualisation, improving patient safety, is cost saving or cost-neutral but is not expected to yield additional costs. These results endorse implementing DPYD screening before start of fluoropyrimidine treatment as standard of care.

Cost-analysis, Dihydropyrimidine dehydrogenase, DPYD, Fluoropyrimidines, Genotyping, Pharmacogenetics, Toxicity,
European Journal of Cancer
Department of Medical Oncology

Henricks, L.M. (Linda M.), Lunenburg, C.A.T.C. (Carin A.T.C.), de Man, F.M, Meulendijks, D, Frederix, G.W.J, Kienhuis, E, … Schellens, J.H.M. (Jan H.M.). (2019). A cost analysis of upfront DPYD genotype–guided dose individualisation in fluoropyrimidine-based anticancer therapy. European Journal of Cancer, 107, 60–67. doi:10.1016/j.ejca.2018.11.010