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 - Dezentje, 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, Marlene H. W.
AU - Mandigers, Caroline M. P. W.
AU - Rosing, Hilde
AU - Beijnen, Jos H.
AU - van Werkhoven, Erik
AU - van Kuilenburg, Andre 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 - Funding Information:
LMH, CATCL and the NCT02324452 study were sponsored by the Dutch Cancer Society (Alpe-d′HuZes/KWF-fund, NKI2013-6249). CATCL was previously supported by an unrestricted grant from Roche Pharmaceuticals. There was no involvement in the study design, data collection, analysis, interpretation, writing of the report or decision to submit for publication by any of the funding sources.
Funding Information:
LMH, CATCL and the NCT02324452 study were sponsored by the Dutch Cancer Society (Alpe-d′HuZes/KWF-fund, NKI2013-6249 ). CATCL was previously supported by an unrestricted grant from Roche Pharmaceuticals . There was no involvement in the study design, data collection, analysis, interpretation, writing of the report or decision to submit for publication by any of the funding sources.
Publisher Copyright:
© 2018 Elsevier Ltd
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 (sic)2599 per patient compared with (sic)2650 for non-screening, resulting in a net cost saving of (sic)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. (C) 2018 Elsevier Ltd. All rights reserved.
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 (sic)2599 per patient compared with (sic)2650 for non-screening, resulting in a net cost saving of (sic)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. (C) 2018 Elsevier Ltd. All rights reserved.
KW - Cost-analysis
KW - Dihydropyrimidine dehydrogenase
KW - DPYD
KW - Pharmacogenetics
KW - Fluoropyrimidines
KW - Genotyping
KW - Toxicity
KW - FLUOROURACIL PLUS LEUCOVORIN
KW - METASTATIC COLORECTAL-CANCER
KW - ORAL CAPECITABINE
KW - TOXICITY
KW - 5-FLUOROURACIL
KW - DEFICIENCY
KW - PREDICTOR
U2 - 10.1016/j.ejca.2018.11.010
DO - 10.1016/j.ejca.2018.11.010
M3 - Article
SN - 0959-8049
VL - 107
SP - 60
EP - 67
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -