Implementation of DPYD and UGT1A1 Testing in Patients With GI Cancer: A Prospective, Nonrandomized Clinical Trial

To determine the feasibility and effectiveness of implementing pretreatment DPYD/UGT1A1 testing in patients with gastrointestinal cancer and its impact compared with a biobank population. A prospective, nonrandomized implementation trial of pretreatment DPYD/UGT1A1 testing with preemptive dose reduction was conducted in patients initiating treatment with a fluoropyrimidine (FP, [fluorouracil or capecitabine]) or irinotecan. The primary end point was feasibility, defined as proportion of results available prior to cycle 1 of treatment. Secondarily, occurrence of severe treatment-related adverse events (TRAEs), defined as toxicity resulting in hospitalization or emergency department visit, was compared with a biobank population receiving standard dose chemotherapy. Of the 288 patients prospectively tested, 225 (median age 60.7 years, 54% male, 18% Black, 47% colorectal cancer) received a qualifying chemotherapy. Eight of 11 DPYD variant carriers received an FP and eight of 39 UGT1A1 poor metabolizers received irinotecan. The median test turnaround time was 10 days (IQR, 9-13) with 57.4% of results available before cycle 1. Eleven of 16 (69%) participants with a drug-gene interaction (DGI) had results available before chemotherapy initiation and received pharmacogenetic-recommended dose reductions. Compared with the biobank cohort (n = 229), the prospective DGI group experienced fewer severe TRAEs (38% v 65%, P = .123), treatment discontinuations (31% v 47%, P = .356), and treatment modifications (38% v 76%, P = .028). Pretreatment DPYD/UGT1A1 testing and dose reduction was feasible, enabling clinicians to make the appropriate chemotherapy dose reductions, reducing occurrence of adverse outcomes. DPYD/UGT1A1 testing is an important precision oncology approach to optimize patient safety.