Clinician perspectives on preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies.

Abstract

54 Background: 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. Methods: We conducted a multi-site mixed-methods study to understand clinician attitudes toward PGx testing and to identify facilitators and barriers to using preemptive testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a demographic survey and semi-structured interview informed by the Consolidated Framework for Implementation Research. Interviews were analyzed using a modified grounded theory approach. Results: A total of 16 medical oncologists and 9 oncology pharmacists from one academic medical center and two community hospitals participated. Fifteen (60%) participants reported feeling comfortable or very comfortable with interpreting PGx test results. While clinicians expressed generally favorable attitudes toward PGx testing, many were hesitant to use it to preemptively guide chemotherapy dosing due to a perceived lack of evidence for this practice. They cited a lack of consensus chemotherapy dosing recommendations in response to PGx test results, as well as concerns about decreased drug efficacy, especially in patients treated with curative intent. Additional barriers included 1) a low prevalence of actionable PGx variants; 2) lengthy PGx test turnaround time; 3) concerns about testing costs and lack of insurance coverage; and 4) burdensome integration of PGx testing into clinical workflows. The electronic health record emerged as a potential tool for the unobtrusive integration of PGx testing into clinical practice–suggested applications included default PGx test orders for eligible patients, discrete reporting of PGx variant results, and clinical decision support to guide subsequent chemotherapy dosing. Conclusions: Successful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multi-level effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study. The electronic health record should be explored as a tool to integrate PGx testing into routine practice.