Therapeutic Advances in Medical Oncology (Dec 2020)

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

  • Natalie Reizine,
  • Everett E. Vokes,
  • Ping Liu,
  • Tien M. Truong,
  • Rita Nanda,
  • Gini F. Fleming,
  • Daniel V.T. Catenacci,
  • Alexander T. Pearson,
  • Sandeep Parsad,
  • Keith Danahey,
  • Xander M. R. van Wijk,
  • Kiang-Teck J. Yeo,
  • Mark J. Ratain,
  • Peter H. O’Donnell

DOI
https://doi.org/10.1177/1758835920974118
Journal volume & issue
Vol. 12

Abstract

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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.