Global Investigation of Clinical Implementation Strategies for DPYD Testing to Guide Fluoropyrimidine Therapy

Abstract

Fluoropyrimidines are a vital component of chemotherapy regimens. Deleterious DPYD variants reduce activity of dihydropyrimidine dehydrogenase, the rate-limiting enzyme of fluoropyrimidine catabolism, resulting in reduced fluoropyrimidine clearance and elevated risk of life-threatening toxicities. DPYD genotype-guided fluoropyrimidine therapy can mitigate the risk of severe life-threatening toxicities, but adoption of testing globally has been limited. We developed a 91-item survey investigating global DPYD implementation strategies to gain insight into common practices and successful strategies. The survey was disseminated to Pharmacogenomics Global Research Network Implementation Working Group members consisting of 54 health care sites across 15 countries. Survey responses were received from 28 sites (52%) across 9 countries. Over 80% of sites implemented, or planned to implement, a preemptive testing strategy (i.e., before a fluoropyrimidine is administered) leveraging the electronic health record (EHR) to disseminate DPYD results to providers. All sites created infrastructure to support DPYD testing (e.g., order sets, EHR decision support), but 70% of sites indicated reliance on clinicians to remember test ordering. Only 2 sites reported high DPYD testing rates (> 75%) among patients planned to receive a fluoropyrimidine. Most sites (57%) used in-house clinical laboratories that tested for the majority of DPYD Tier 1 variants. Among sites that had implemented DPYD testing, the median turnaround time was 10 days. Few sites indicated that a high percentage (> 75%) of DPYD results were returned before fluoropyrimidine administration. Our results suggest that additional implementation strategies are needed, addressing barriers and facilitators of DPYD testing.