Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation

Kelsey S Lau-Min,Lisa A Varughese,Sony Tuteja,Randall A Oyer,Ursina R Teitelbaum,Christine Cambareri,Nandi J Reddy,Maria N Nelson

doi:10.1186/s12885-022-09171-6

Abstract

BackgroundPharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice.MethodsWe conducted a qualitative study of oncology clinicians to identify barriers to using preemptive PGx testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a semi-structured interview informed by the Consolidated Framework for Implementation Research (CFIR). Interviews were analyzed using an inductive content analysis approach.ResultsParticipants included sixteen medical oncologists and nine oncology pharmacists from one academic medical center and two community hospitals in Pennsylvania. Barriers to the use of preemptive PGx testing to guide chemotherapy dosing mapped to four CFIR domains: intervention characteristics, outer setting, inner setting, and characteristics of individuals. The most prominent themes included 1) a limited evidence base, 2) a cumbersome and lengthy testing process, and 3) a lack of insurance coverage for preemptive PGx testing. Additional barriers included clinician lack of knowledge, difficulty remembering to order PGx testing for eligible patients, challenges with PGx test interpretation, a questionable impact of preemptive PGx testing on clinical care, and a lack of alternative therapeutic options for some patients found to have actionable PGx variants.ConclusionsSuccessful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multifaceted effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study.

Highlights

Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively
Prospective studies have demonstrated that preemptive genotyping for DPYD variants can reduce chemotherapy-related toxicity and improve patient safety, and many guidelines recommend that patients with DPYD or UGT1A1 variants should undergo genotype-guided dose reductions when treated with fluoropyrimidines or irinotecan [2, 4,5,6,7]
Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in practice

Summary

Introduction

Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice. Fluoropyrimidines such as 5-fluorouracil (5-FU) and capecitabine form the backbone of chemotherapeutic treatment for gastrointestinal malignancies, often in conjunction with irinotecan and/or oxaliplatin. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in practice. We conducted a qualitative study of oncology clinicians to identify barriers to using PGx testing to guide chemotherapy dosing in patients with gastrointestinal malignancies

Methods

Results

Discussion

Conclusion