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Considerations for the clinical implementation of DPYD and UGT1A1-guided chemotherapy
Mary-Pearl Ojukwu1, Carlos Vegas1, Emily J Cicali1
1Center for Pharmacogenomics and Precision Medicine and Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Abstract:
Existing literature demonstrates the benefits of DPYD and UGT1A1 pharmacogenetic (PGx) testing to reduce toxicity from fluoropyrimidines and irinotecan, respectively. The Food and Drug Administration (FDA) has provided UGT1A1-guided irinotecan dosing for 20 years, and in 2025, the FDA and National Comprehensive Cancer Network both updated their guidance to recommend DPYD testing prior to fluoropyrimidine therapy. As such, there is an increasing interest in testing and a need for guidance describing implementation strategies. This review summarizes conclusions from DPYD and/or UGT1A1 implementation initiatives and describes key takeaways related to perspectives, workflow, cost, and supportive care from 32 included articles. Perspectives toward testing were generally positive, although barriers such as turnaround time and cost concerns were still identified. Workflow integration varied by institution, but a clear delineation of duties was consistently necessary. For both DPYD and UGT1A1, real-world studies and modeling data indicate testing is cost-effective. PGx testing was underutilized for supportive care medications despite its relevance, but there is an opportunity to leverage panel-based approaches to increase utilization without additional workflow burden. Description of these key considerations and takeaways reported by those implementing DPYD and/or UGT1A1 PGx testing would be beneficial to institutions in the early phases of implementation.
Insights
Pharmacogenetic (PGx) testing for DPYD and UGT1A1 is crucial for reducing chemotherapy toxicity. Implementation strategies are vital for widespread adoption, with cost-effectiveness and workflow integration being key considerations.
Area of Science:
- Pharmacogenomics
- Clinical Chemistry
- Translational Medicine
Background:
- DPYD and UGT1A1 pharmacogenetic (PGx) testing reduces fluoropyrimidine and irinotecan toxicity, respectively.
- Regulatory bodies (FDA) and professional organizations (NCCN) now recommend DPYD testing before fluoropyrimidine therapy.
- Growing interest in PGx testing necessitates guidance on implementation strategies.
Purpose of the Study:
- To review conclusions from DPYD and/or UGT1A1 implementation initiatives.
- To identify key takeaways regarding perspectives, workflow, cost, and supportive care.
- To provide guidance for institutions implementing PGx testing.
Main Methods:
- Systematic review of 32 articles on DPYD and/or UGT1A1 implementation initiatives.
- Analysis of data related to perspectives, workflow, cost, and supportive care.
- Synthesis of key considerations and takeaways from implementation studies.
Main Results:
- Positive perspectives towards PGx testing, but barriers like turnaround time and cost exist.
- Varied workflow integration across institutions, necessitating clear duty delineation.
- Real-world data and modeling confirm cost-effectiveness of DPYD and UGT1A1 testing.
- Underutilization of PGx testing for supportive care medications presents an opportunity for panel-based approaches.
Conclusions:
- Implementation of DPYD and UGT1A1 PGx testing is feasible and beneficial.
- Addressing barriers and optimizing workflow are crucial for successful implementation.
- Panel-based PGx testing can enhance utilization for supportive care without increasing workflow burden.
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