Implementing DPYD genotyping to predict chemotherapy toxicity in Australia: a feasibility study

Area of Science:

• Pharmacogenomics
• Oncology
• Clinical Chemistry

Background:

• Implementing pharmacogenomic-guided cancer treatment presents challenges in equitable and effective large-scale application.
• DPYD genotyping identifies patients at risk of severe fluoropyrimidine (FP) toxicity, a common chemotherapy regimen in Australia.
• Current Australian practice has not formally adopted DPYD variant screening despite international standardization.

Purpose of the Study:

• To determine the genotyping turnaround time (TAT) for four key DPYD variants in Australian patients.
• To identify fluoropyrimidine toxicities in DPYD variant carriers.
• To analyze healthcare stakeholder perspectives on implementing DPYD genotyping, including barriers and enablers.

Main Methods:

• Real-Time Polymerase Chain Reaction (PCR) was used for DPYD variant genotyping.
• Qualitative data on stakeholder perspectives were collected through semi-structured questionnaires.

Main Results:

• A mean TAT of 7.2 days (5.2 business days) was achieved for 104 patients over 24 months.
• 9 out of 16 DPYD variant carriers experienced grade 3-4 toxicity, including ICU admissions and one death.
• Key barriers to implementation included clinical environment and resources, while motivation to improve patient care was a primary enabler.

Conclusions:

• DPYD genotyping is a feasible strategy for enhancing precision oncology in patients receiving FP chemotherapies.
• A 7-day TAT is considered acceptable by stakeholders and national oncology groups.
• This pilot study provides crucial data for a national project assessing the impact of DPYD genotyping on FP tolerability, patient safety, and cost-effectiveness in Australia.