Implementing DPYD*2A Genotyping in Clinical Practice: The Quebec, Canada, Experience.

Area of Science:

• Pharmacogenomics
• Clinical Chemistry
• Oncology

Background:

• Fluoropyrimidines are crucial in combination cancer chemotherapy.
• Dihydropyrimidine dehydrogenase (DPD) deficiency can cause severe, life-threatening toxicities.
• The DPYD*2A polymorphism is a well-studied genetic variant associated with DPD deficiency.

Purpose of the Study:

• To evaluate the impact of integrating DPYD*2A genetic testing into routine clinical practice.
• To assess the feasibility and outcomes of upfront DPYD genotyping before fluoropyrimidine-based chemotherapy.

Main Methods:

• Retrospective chart review of patients with heterozygous or homozygous DPYD*2A mutations in Quebec, Canada.
• Analysis of DPYD*2A testing results and subsequent clinical outcomes over a 17-month period.
• Comparison of outcomes between patients tested upfront versus those identified after experiencing toxicities.

Main Results:

• Out of 2,617 patients tested, 25 (0.95%) had a DPYD*2A mutation (24 heterozygous, 1 homozygous), all of White ethnicity.
• Fifteen patients received upfront DPYD testing, while five were identified post-toxicity.
• Patients receiving reduced chemotherapy doses based on upfront DPYD*2A testing experienced no severe toxicities (grade ≥3).
• DPYD*2A test results were available within an average of 6 days, without delaying treatment initiation.

Conclusions:

• Upfront DPYD genotyping is a feasible strategy in clinical practice to prevent severe toxicities and hospitalizations.
• Administering fluoropyrimidine chemotherapy at reduced doses is safe for patients heterozygous for the DPYD*2A mutation.
• Systematic DPYD genotyping before treatment can optimize cancer therapy and patient safety.