Implementation of <i>DPYD</i> and <i>UGT1A1</i> Testing in Patients With GI Cancer: A Prospective, Nonrandomized Clinical Trial.

Abstract

To determine the feasibility and effectiveness of implementing pretreatment <i>DPYD/UGT1A1</i> testing in patients with gastrointestinal cancer and its impact compared with a biobank population. A prospective, nonrandomized implementation trial of pretreatment <i>DPYD/UGT1A1</i> 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% <i>v</i> 65%, <i>P</i> = .123), treatment discontinuations (31% <i>v</i> 47%, <i>P</i> = .356), and treatment modifications (38% <i>v</i> 76%, <i>P</i> = .028). Pretreatment <i>DPYD/UGT1A1</i> testing and dose reduction was feasible, enabling clinicians to make the appropriate chemotherapy dose reductions, reducing occurrence of adverse outcomes. <i>DPYD/UGT1A1</i> testing is an important precision oncology approach to optimize patient safety.