PI-031 - PILOT, FEASIBILITY TESTING OF DPYD AND UGT1A1 PRIOR TO CHEMOTHERAPY IN A COMMUNITY-BASED CANCER CENTER.

N. El Rouby¹, J. Grund², M. Muldoon², K. Hesse², M. Beck², M. Frimpong-Manso³, J. Allen², B. Phillips²; ¹University of Cincinnati, Cincinnati, OH, USA, ²St. Elizabeth Healthcare, Edgewood, KY, USA, ³PharMerica, Louisville, KY, USA.

Background: Fluoropyrimidines [FPD] (fluorouracil and capecitabine) and irinotecan are commonly used chemotherapy agents in a wide variety of cancers, with recognized toxicity. Testing for common variants in DPYD and UGT1A1 is critical for genotype-guided dosing and prevention of severe side effects, yet still not widely adopted. We piloted clinical testing of DPYD and UGT1A1 in patients planned to start fluoropyrimidine (FPD) and/or irinotecan-based treatment in a community cancer center.

Methods: Testing via buccal swab started in November 2020 using a multi-gene panel through an external clinical lab. DPYD was tested for *2A, *13, and rs67376798 while UGT1A1 was tested for *28 and *6. Actionable phenotypes include DPYD variant carriers and/or UGT1A1 Poor Metabolizers (PMs). A pharmacist reviewed the genetic results and communicated dose changes on actionable phenotypes who received the relevant drugs. Data were collected on 216 patients. The prevalence of actionable phenotypes (actionable phenotype/ 216) and the proportion of pre-treatment, genotype-guided dose changes (dose changes/actionable phenotypes with a relevant drug) were calculated.

Results: Fourteen percent of patients (n=30/216) had an actionable phenotype for either DPYD (n=4) or UGT1A1 (n=26). Four DPYD Intermediate Metabolizers (IMs) and five UGT1A1 PMs received either a FPD or irinotecan-based regimen, respectively. Dose changes were implemented in 100% of DPYD IMs (n=4/4) who received an FPD drug and 60% of UGT1A1 PMs (N=3/5) who received irinotecan.

Conclusion: Pharmacogenetic testing of DPYD and UGT1A1 is feasible, with 77% pre-treatment genotype dose changes. More education is needed as we expand our testing to increase the uptake of recommendations, especially related to UGT1A1-irinotecan interaction.

Henricks LM, Lunenburg CATC, de Man FM, Meulendijks D, Frederix GWJ, Kienhuis E, et al. DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol. 2018. PMID: 30348537.

Toffoli G, Cecchin E, Gasparini G, D'Andrea M, Azzarello G, Basso U, et al. Genotype-driven phase I study of irinotecan administered in combination with fluorouracil/leucovorin in patients with metastatic colorectal cancer. J Clin Oncol. 2010 PMID: 20038727.