Page 180 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 6
Abstract
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 (DPD), the main metabolic fluoropyrimidine enzyme, primarily caused by genetic DPYD polymorphisms. In a large prospective study, it was concluded that upfront DPYD-guided dose individualization is able to improve safety of fluoropyrimidine-based therapy. In our current analysis, we evaluated whether this strategy is cost-saving.
A cost-minimization 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, hospitalization 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.
Expected total costs of the screening strategy were €2,599 per patient, compared to €2,650 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.
Upfront DPYD-guided dose individualization, 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.
Acknowledgements
All 17 participating centers are acknowledged for their contribution to patient inclusion. We thank dr. Maarten Deenen for providing his previously developed cost model (Deenen et al. J Clin Oncol 2016) and his input to the study.
178