TY - JOUR
T1 - A cost analysis of upfront DPYD genotype-guided dose individualisation in fluoropyrimidine-based anticancer therapy
AU - Henricks, Linda M
AU - Lunenburg, Carin A T C
AU - de Man, Femke M
AU - Meulendijks, Didier
AU - Frederix, Geert W J
AU - Kienhuis, Emma
AU - Creemers, Geert-Jan
AU - Baars, Arnold
AU - Dezentjé, Vincent O
AU - Imholz, Alexander L T
AU - Jeurissen, Frank J F
AU - Portielje, Johanna E A
AU - Jansen, Rob L H
AU - Hamberg, Paul
AU - Ten Tije, Albert J
AU - Droogendijk, Helga J
AU - Koopman, Miriam
AU - Nieboer, Peter
AU - van de Poel, Marlène H W
AU - Mandigers, Caroline M P W
AU - Rosing, Hilde
AU - Beijnen, Jos H
AU - van Werkhoven, Erik
AU - van Kuilenburg, André B P
AU - van Schaik, Ron H N
AU - Mathijssen, Ron H J
AU - Swen, Jesse J
AU - Gelderblom, Hans
AU - Cats, Annemieke
AU - Guchelaar, Henk-Jan
AU - Schellens, Jan H M
N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - cost-analysis
KW - dihydropyrimidine dehydrogenase
KW - DPYD
KW - pharmacogenetics
KW - fluoropyrimidines
KW - genotyping
KW - toxicity
U2 - 10.1016/j.ejca.2018.11.010
DO - 10.1016/j.ejca.2018.11.010
M3 - Article
C2 - 30544060
SN - 0959-8049
VL - 107
SP - 60
EP - 67
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -