A cost analysis of upfront DPYD genotype-guided dose individualisation in fluoropyrimidine-based anticancer therapy

Linda M Henricks, Carin A T C Lunenburg, Femke M de Man, Didier Meulendijks, Geert W J Frederix, Emma Kienhuis, Geert-Jan Creemers, Arnold Baars, Vincent O Dezentjé, Alexander L T Imholz, Frank J F Jeurissen, Johanna E A Portielje, Rob L H Jansen, Paul Hamberg, Albert J Ten Tije, Helga J Droogendijk, Miriam Koopman, Peter Nieboer, Marlène H W van de Poel, Caroline M P W MandigersHilde Rosing, Jos H Beijnen, Erik van Werkhoven, André B P van Kuilenburg, Ron H N van Schaik, Ron H J Mathijssen, Jesse J Swen, Hans Gelderblom, Annemieke Cats, Henk-Jan Guchelaar, Jan H M Schellens

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)60-67
Number of pages8
JournalEuropean Journal of Cancer
Volume107
DOIs
Publication statusPublished - Jan 2019

Keywords

  • cost-analysis
  • dihydropyrimidine dehydrogenase
  • DPYD
  • pharmacogenetics
  • fluoropyrimidines
  • genotyping
  • toxicity

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