Page 184 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 6
carriers, 16 DPYD*2A carriers and one c.1679T>G carrier. Details on patient characteristics, treatment and toxicity incidence are published separately.11 In short, 33 out of 85 DPYD variant allele carriers (39%) experienced grade ≥3 treatment-related toxicity, while this was significantly lower in the group of wild-type patients with 231 out of 1,018 patients (23%) experiencing severe toxicity (p=0.001). Compared to the historical cohort of DPYD variant allele carriers treated with full dose, DPYD genotype-guided dosing markedly decreased the risk of severe fluoropyrimidine-related toxicity for three out of four variants (DPYD*2A, c.1679T>G and c.2846A>T; Figure 2). No reduction in severe treatment-related toxicity was shown for c.1236G>A.
Figure 2. Relative risk for severe treatment-related toxicity of DPYD variant allele carriers receiving dose-reduction (this study) and DPYD variant allele carriers treated with full dose (historical cohort) The relative risk for overall grade ≥3 fluoropyrimidine-related toxicity compared to non-carriers of this variant was calculated with data from this study11 and for the historical cohort with data derived from a previously published random-effects meta-analysis.8 Unadjusted relative risks for the meta-analysis are depicted, as the relative risk in the current study was also calculated as an unadjusted value. For c.1679T>G no relative risk could be calculated in this study, as only one patient who carried c.1679T>G was present. This patient did not experience severe toxicity.
Abbreviations: 95%CI: 95% confidence interval.
Cost analysis
All parameter estimates used in the model are provided in Table 1. In the cost analysis the expected total costs for the screening strategy were €2,599 per patient, compared to €2,650 per patient for the non-screening strategy, resulting in a net cost-saving of €51 per patient treated.
Results of the one-way sensitivity analysis are depicted in Figure 3, demonstrating that the frequency of the DPYD variant allele genotype had the largest influence on outcome of the cost analysis, followed by the risk of hospitalization at the nursing ward for DPYD variant
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