JCO Precis Oncol

Pretreatment pharmacogenetic testing reduces toxicity in GI cancer chemotherapy

August 13, 2025

Study details: This prospective, nonrandomized implementation trial (IMPACT-GI) evaluated the feasibility and clinical utility of pretreatment DPYD and UGT1A1 pharmacogenetic testing in 288 patients with GI cancers initiating fluoropyrimidine or irinotecan therapy. Primary endpoint was feasibility, defined as the proportion of test results available before cycle 1. Secondary endpoints included severe treatment-related adverse events (TRAEs), treatment discontinuations, and modifications, compared with a biobank control cohort.

Results: Of 225 patients who received qualifying chemotherapy, 69% of those with actionable drug-gene interactions had results available pre-treatment and received genotype-guided dose reductions. Compared with the biobank cohort, the tested group had fewer severe TRAEs (38% vs. 65%), fewer treatment discontinuations (31% vs. 47%), and fewer modifications (38% vs. 76%).

Clinical impact: The findings demonstrate that implementing DPYD and UGT1A1 testing is feasible and clinically beneficial, enabling safer chemotherapy dosing. It supports broader adoption of pharmacogenetic testing to reduce toxicity and improve outcomes in GI cancer care.

Source:

Tuteja S, et al. (2025, August 7). JCO Precis Oncol. Implementation of DPYD and UGT1A1 Testing in Patients With GI Cancer: A Prospective, Nonrandomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/40773711/