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Overall, DPYD-guided fluoropyrimidine dosing adjustments did not adversely impact progression-free survival (PFS) and overall survival (OS) in DPYD variant carriers; however, a subgroup analysis identified compromised PFS specifically in c.1236G>A variant carriers.

The following is a summary of “Survival of Patients With Cancer With DPYD Variant Alleles and Dose-Individualized Fluoropyrimidine Therapy—A Matched-Pair Analysis,” published in the December 2023 issue of Oncology by Knikman, et al.

For a study, researchers sought to discern the impact of DPYD-guided fluoropyrimidine dosing on the progression-free survival (PFS) and overall survival (OS) in individuals who carry DPYD variant alleles. The primary objective was to compare the treatment outcomes between DPYD variant carriers receiving a reduced dose and those without the variant receiving the standard fluoropyrimidine dose.

Data was extracted from a comprehensive multicenter study. The study encompassed DPYD variant carriers who were administered either a 25% reduced dose due to specific variant alleles (c.1236G>A and c.2846A>T) or a 50% reduced dose for specific variants (DPYD*2A and c.1679T>G). Additional data from DPYD variant carriers treated with similarly reduced doses in routine clinical scenarios were also incorporated. Each DPYD variant carrier was meticulously paired with three DPYD wild-type controls who received a standard dose. Survival analyses were executed using Kaplan-Meier estimates complemented by Cox regression.

The dataset comprised 156 DPYD variant carriers juxtaposed against 775 DPYD wild-type controls. Within this cohort, specific subsets of variant carriers were identified, with 93 being pooled together for analysis. The findings revealed that for the pooled DPYD variant carriers, there was no detrimental impact on PFS (hazard ratio [HR], 1.23; 95% CI, 1.00 to 1.51; P = .053) and OS (HR, 0.95; 95% CI, 0.75 to 1.51; P = .698) due to DPYD-guided dose adjustments. However, a distinct observation was made in the subgroup analysis, indicating a compromised PFS (HR, 1.43; 95% CI, 1.10 to 1.86; P = .007) specifically in c.1236G>A variant carriers. No significant differences were discerned for carriers of DPYD*2A and c.2846A>T variants.

The study’s exploratory findings suggested that employing DPYD-guided fluoropyrimidine dosing did not have an adverse impact on PFS and OS among the combined pool of DPYD variant carriers. Nonetheless, vigilant monitoring coupled with prompt dose adjustments based on emerging toxicities is advised, particularly for individuals with the c.1236G>A variant receiving an initially reduced dose.

Source: ascopubs.org/doi/full/10.1200/JCO.22.02780