Implementation of pharmacogenomic testing in oncology care (PhOCus): study protocol of a pragmatic, randomized clinical trial. (December 2020)

• Record Type: Journal Article
• Authors: Reizine, Natalie; Vokes, Everett E.; Liu, Ping; Truong, Tien M.; Nanda, Rita; Fleming, Gini F.; Catenacci, Daniel V.T.; Pearson, Alexander T.; Parsad, Sandeep; Danahey, Keith; van Wijk, Xander M. R.; Yeo, Kiang-Teck J.; Ratain, Mark J.; O'Donnell, Peter H.
• Is Part Of: Therapeutic advances in medical oncology. Volume 12(2020)
• Publication Date: 2020-12
• Subjects: chemotherapy -- fluoropyrimidines -- genetic testing -- irinotecan -- pharmacogenomics -- toxicity management; Oncology -- Periodicals; Cancer -- Treatment -- Periodicals; 616.994005
• DOI: 10.1177/1758835920974118
• Languages: English
• ISSNs: 1758-8340

Abstract

Background: Many cancer patients who receive chemotherapy experience adverse drug effects. Pharmacogenomics (PGx) has promise to personalize chemotherapy drug dosing to maximize efficacy and safety. Fluoropyrimidines and irinotecan have well-known germline PGx associations. At our institution, we have delivered PGx clinical decision support (CDS) based on preemptively obtained genotyping results for a large number of non-oncology medications since 2012, but have not previously evaluated the utility of this strategy for patients initiating anti-cancer regimens. We hypothesize that providing oncologists with preemptive germline PGx information along with CDS will enable individualized dosing decisions and result in improved patient outcomes. Methods: Patients with oncologic malignancies for whom fluoropyrimidine and/or irinotecan-inclusive therapy is being planned will be enrolled and randomly assigned to PGx and control arms. Patients will be genotyped in a clinical laboratory across panels that include actionable variants in UGT1A1 and DPYD . For PGx arm patients, treating providers will be given access to the patient-specific PGx results with CDS prior to treatment initiation. In the control arm, genotyping will be deferred, and dosing will occur as per usual care. Co-primary endpoints are dose intensity deviation rate (the proportion of patients receiving dose modifications during the first treatment cycle), and grade ⩾3 treatment-related toxicities throughout the treatment course. Additional study endpoints will include cumulative drug dose intensity, progression-free survival, dosing of additional PGx supportive medications, and patient-reported quality of life and understanding of PGx. Discussion: Providing a platform of integrated germline PGx information may promote personalized chemotherapy dosing decisions and establish a new model of care to optimize oncology treatment planning.