Matched-pair analysis of survival of patients with cancer with DPYD variants receiving dose-individualized fluoropyrimidine therapy

DPYD-guided fluoropyrimidine (FP) dosing improves patient safety in carriers of DPYD variant alleles. The impact on treatment outcome in these patients is largely unkown. A retrospective multicenter study in The Netherlands compared progression-free survival and overall survival between DPYD variant carriers treated with a reduced FP dose and DPYD wild-type controls receiving full FP dose. The study found that DPYD-guided FP dosing did not negatively affect PFS and OS in pooled DPYD variant carriers. However, PFS for c.1236G>A treated with a 25% reduced dose was significantly shorter when compared with DPYD wild-type patients receiving a full dose. The authors conclude that reducing FP dose for patients who are carriers of pathogenic DPYD variants does not appear to compromise treatment efficacy, although close monitoring and early dose modifications are recommended when treating c.1236G>A variant carriers with a reduced starting dose.