Pharmacogenomic potential in advanced cancer patients

• Published in: American journal of health-system pharmacy 2019-03, Vol.76 (7), p.415-423
• Main Authors: Nichols, Dan, Arnold, Susanne, Weiss, Heidi L, Wu, Jianrong, Durbin, Eric B, Miller, Rachel, Kolesar, Jill
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - antagonists & inhibitors; Biomarkers, Tumor - genetics; Capecitabine - pharmacology; Capecitabine - therapeutic use; Clinical Research Report; Drug Prescriptions - statistics & numerical data; Female; Humans; Male; Middle Aged; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - pathology; Ondansetron - pharmacology; Ondansetron - therapeutic use; Pharmacogenomic Testing; Pharmacogenomic Variants; Precision Medicine - statistics & numerical data; Prospective Studies; Retrospective Studies; Sertraline - pharmacology; Sertraline - therapeutic use
• ISSN: 1079-2082; 1535-2900
• DOI: 10.1093/ajhp/zxy079

Abstract Purpose The prevalence of pharmacogenetically actionable medications in advanced cancer patients whose therapy may be optimized with genotype data was determined. Methods Patients enrolled in our institutional molecular tumor board observational cohort were included in this study. Collected data included demographics, type(s) of cancer, and outpatient medications. Medications were classified as “pharmacogenetically actionable” if there are Clinical Pharmacogenetics Implementation Consortium (CPIC) therapeutic recommendations for that medication based on the presence of germline variations. The prevalence of pharmacogenetically actionable medications in the study population was determined, and the frequency of opportunities for pharmacogenetic prescribing and adverse event (AE) mitigation were estimated. Results In a cohort of 193 patients with advanced cancer, 65% of patients were taking a pharmacogenetically actionable medication. Approximately 10% of the outpatient medications taken by the study population had a pharmacogenetic association. The most common pharmacogenetically actionable medications being used were ondansetron (47%), capecitabine (10%), and sertraline (7%). Using published genetic variation frequencies and AE risk, we conservatively estimated that 7.1% of cancer patients would be eligible for genetic-based medication adjustment, and 101 AEs would be prevented in 10,000 patients genotyped. Conclusion Medications with pharmacogenetic associations are used commonly in the advanced cancer patient population. This widespread exposure supports the implementation of prospective genotyping in the treatment of these high-risk patients.