Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Feasibility of DPYD Genotype-guided personalised Fluoropyrimidine dosing (#241)

Cass White 1 , Christine Paul 1 , Rodney Scott 1 2 , Stephen Ackland 1
  1. College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
  2. Molcular Medicine, Pathology North, John Hunter Hospital, , New Lambton Heights, New South Wales, Australia

Approximately 10,000 Australians require fluoropyrimidine chemotherapies (FP) for solid organ cancers per annum. Serious toxicities resulting in hospitalisation and even death can follow exposure to FP chemotherapy in ~10% patients who are deficient in Dihydropyrimidine Dehydrogenase (DPD), the enzyme critical for FP metabolism. Genotyping DPYD, encoding DPD, can identify deficient patients and allow for prospective FP dose adjustment. AIM AND METHOD: We determine turn-around-time (TAT) for DPYD genotyping. Patients with solid organ cancers (GI, breast, head and neck) aged 18 and older who were intended to receive, currently receiving or recently completed FP chemotherapy were eligible. Blood samples were collected and genotyped at John Hunter Hospital. Samples were genotyped via quantitative Real-Time PCR amplification to identify pre-determined DPYD variants c.1905+1G>A, c.2846A>T, c.1679T>G and c.1236G>A/HapB3. Genotype-guided dose adjustment is based upon international consortia dose-adjustment guidelines at clinician discretion. RESULTS: Seventy-five patients were recruited across four participating centres in regional NSW. Samples were batched and analysed weekly by a PhD student. Variants were identified in 12/75 patients (16%); 7 c.1236G>A, 3 c.1905+1G>A, 1 c.1679T>G and 1 c.2846A>T. All carriers were heterozygous for the specified variants. Mean TAT was 6.5 days, comparable to European data. TAT could be markedly reduced if PCR testing could be offered more than once a week. Prevalence of DPYD mutations in this cohort was higher than baseline population data (~8%), but this explainable by clinician bias in the selection of patients already experiencing toxicities for inclusion in this study. CONCLUSION: DPYD genotyping provides a functional example of pharmacogenomic screening. It is already recommended internationally across Europe as a cost-effective means of reducing toxicity rates and improving toxicity management. This study confirms that results can be provided to clinicians in a timely manner. Further analyses are needed to comprehensively understand the impact of DPYD genotyping within the Australian system.