Real‐world implementation of DPYD and UGT1A1 pharmacogenetic testing in a community‐based cancer center

Abstract

We set out to demonstrate the feasibility of pharmacogenetic testing of DPYD and UGT1A1 and explore the clinical benefits in a community‐based cancer center. We conducted a retrospective review of 280 patients who underwent pharmacogenetic testing between November 2020 and May 2023. The primary end points included the percentage of patients with results prior to chemotherapy initiation, percentage of DPYD‐ and UGT1A1‐guided interventions implemented before chemotherapy initiation, and the turnaround time (TAT) for the pharmacogenetics results. Exploratory end points included a comparison of unplanned hospitalizations and treatment interruptions among (1) DPD phenotypes in patients who received fluoropyrimidines and (2) UGT1A1 phenotypes in patients who received irinotecan ± fluoropyrimidines. We evaluated cancer progression among patients who received DPYD‐guided dose reductions in the curative setting. More than 75% of patients had results prior to initiation of chemotherapy and 61.5% of the actionable interventions were implemented before chemotherapy, with a median TAT of 7 calendar days (IQR 5–8 calendar days). A non‐significant higher percentage of unplanned hospitalizations and treatment interruptions occurred among patients with normal DPYD compared with patients with DPYD‐guided dose reductions. A non‐significant higher frequency of treatment interruptions and dose reductions were observed in UGT1A1 intermediate metabolizer (IM) compared with UGT1A1 normal metabolizer (NM). None of the patients who received DPYD‐guided dose reductions in the curative setting experienced progression after a median follow‐up of 342 days. The real‐world evidence generated from this study demonstrates the feasibility of pre‐chemotherapy pharmacogenetic testing of DPYD and UGT1A1 in a community‐based cancer center.

Strategies for DPYD Testing Prior to Fluoropyrimidine Chemotherapy in the United States

“…Academic teaching institutions/hospitals comprised >70% of the sites that conducted pre-treatment DPYD testing. Relative to community oncology clinics, these tertiary cancer centers typically have greater access to nancial and technical resources and PGx expertise [13,31,32]. These resources are critical to implementing robust system-wide strategies for clinical PGx adoption including interruptive alerts in the EMR [13], or integrating testing into medication order sets [13,31,32].…”

“…Relative to community oncology clinics, these tertiary cancer centers typically have greater access to nancial and technical resources and PGx expertise [13,31,32]. These resources are critical to implementing robust system-wide strategies for clinical PGx adoption including interruptive alerts in the EMR [13], or integrating testing into medication order sets [13,31,32]. A recent study from Dana-Farber Cancer Institute reported an increase in pre-treatment DPYD testing frequency from 14% to 89% after implementing a system-wide testing program that included automated interruptive alerts at the time of initial FP chemotherapy order [31].…”

“…In our survey, >50% of respondents utilized commercial laboratories for DPYD testing, compared to ~40% using in-house testing. The widespread use of commercial labs may be partially due to improved TAT; ~90% of sites reported they received results within 10 days, which is fast enough for results to be available prior to FP treatment initiation in most patients [32]. Moreover, commercial DPYD tests have adequate allelic coverage [36,37], with ~90% of sites using tests that include at least the 5 validated DPYD variants carried primarily by patients of European ancestry (i.e., DPYD*2A, DPYD*13, DPYD p.D949V, DPYD HapB3, and DPYD p.Y186C) [5][6][7].…”

“…Consequently, DPYD variants are often identi ed only after severe FP toxicity through reactive testing [23]. However, recent publications have raised awareness of the clinical bene t of pre-treatment DPYD testing [28,29], including evidence that dose reduction in DPYD variant carriers does not reduce treatment e cacy [30], leading to an increase in implementation of pre-treatment DPYD testing [13,31,32]. The objective of this survey is to summarize current approaches to the implementation of DPYD testing prior to FP treatment in the US to inform best practices for broader clinical adoption.…”

Translating real‐world evidence/real‐world data

“…Real‐world data from a cancer patient population that underwent DPYD and UGT1A1 pharmacogenetic testing were the subject for the paper by Muldoon et al. 4 The objective of the retrospective analysis of these RWD was to demonstrate the feasibility of the DPYD and UGT1A1 pharmacogenetic testing prior to starting chemotherapy in these patients, specifically for community‐based cancer centers. Operationally, it was shown that the majority of the pharmacogenomic results were available and interpreted before chemotherapy initiation.…”