e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2020

Feasibility of implementing a pharmacist-led DPYD gene testing service for patients newly commencing 5-fluorouracil or capecitabine. (#339)

Benjamin Lee 1 , Senthil Lingaratnam 1 , Marliese Alexander 1 2 , Danny Rischin 2 3 , Sarah Glewis 1 , Prudence Francis 3 , Michael Jefford 2 3 , Hui Li Wong 3 4 , Jeanne Tie 2 3 4 5 , Michael Michael 2 3
  1. Department of Pharmacy, Peter MacCallum Cancer Centre, Melbourne
  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne
  3. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne
  4. Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne
  5. Department of Medical Oncology, Western Health, Melbourne

Background

Dihydropyrimidine dehydrogenase (DPD) deficient patients are at an increased risk of severe fluoropyrimidine (5-fluorouracil or capecitabine, FP) toxicity, which can sometimes be fatal. Large international studies have demonstrated that routine DPYD gene testing is both feasible and cost effective, however is not currently a standard of care in Australia for patients planned to commence FP-based therapy. This analysis aimed to assess the feasibility of establishing a pharmacist-led DPYD gene testing service, as developed overseas, in an Australian tertiary/quarternary cancer centre.

Methods

Medical oncology consultants, nurse consultants, pathology department and pharmacists were engaged to develop a site-specific DPYD gene testing protocol. Patients planned for FP therapy, without previous FP exposure, were referred to the clinical pharmacogenetics pharmacist, before a blood or buccal swab sample was taken. An external genomics company screened for the five Clinical Pharmacogenetics Implementation Consortium (CPIC) recommended gene variants (c.1905+1G>A, c.1679T>G, c.2846A>T, c.1236G>A and c.557A>G). Dose recommendations based on CPIC guidelines and phenotype were made to the treating clinician. Patients were followed-up for toxicity (graded according to CTCAE v5.0) at 3-5 days post first FP exposure and pre-cycle 2 commencement.

Findings

From 16th December 2019 to 15th July 2020, 188 patients (median age 59 years, 53% female) were planned for FP therapy. Genomic testing did not occur for twelve patients and were excluded. Median time from samples being taken to results becoming available was seven days. 95% (167 of 176 patients) of results were available prior to the planned cycle 1 chemotherapy commencement date. Nine patients experienced at least one grade 3/4 toxicity prior to cycle 2; all had normal metaboliser phenotypes. Six patients with intermediate metaboliser phenotypes and one patient with poor metaboliser phenotype were identified.

Interpretation

A pharmacist-led DPYD gene testing service is feasible and can be readily embedded into an Australian health service.