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

Purpose: To determine the feasibility and effectiveness of implementing pretreatment testing in patients with gastrointestinal cancer and its impact compared with a biobank population.

Materials And Methods: A prospective, nonrandomized implementation trial of pretreatment 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.

Results: 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% 65%, = .123), treatment discontinuations (31% 47%, = .356), and treatment modifications (38% 76%, = .028).

Conclusion: Pretreatment testing and dose reduction was feasible, enabling clinicians to make the appropriate chemotherapy dose reductions, reducing occurrence of adverse outcomes. testing is an important precision oncology approach to optimize patient safety.