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Feasibility of Integrating Panel-Based Pharmacogenomics Testing for Chemotherapy and Supportive Care in Patients With
Pashtoon Murtaza Kasi1, Tyler Koep2, Erica Schnettler2
1Division of Hematology, Oncology and Blood & Bone Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
Introduction:
Pharmacogenomics is about selecting the "right drug in the right amount for the right patient." In metastatic colorectal cancer, germline pharmacogenomics testing presents a unique opportunity to improve outcomes, since the genes dihydropyrimidine dehydrogenase and UDP-glucuronosyltransferase metabolizing the chemotherapy drugs, 5-fluorouracil, and irinotecan are already well known. In a retrospective analysis of the landmark TRIBE clinical trial [(TRIBE - TRIplet plus BEvacizumab multicenter, phase III trial by the Italian Cooperative GONO (Gruppo Oncologico Nord Ovest) group (NCT00719797)], the proportion of patients with serious adverse events was higher in those with dihydropyrimidine dehydrogenase/UDP-glucuronosyltransferase aberrations and was dose dependent. We aimed to report on the feasibility and the results of incorporating pharmacogenomics testing into clinical practice.
Methods:
As a quality improvement initiative and a center of individualized medicine grant, we integrated the use of OneOme RightMed comprehensive test, which reports on 27 genes related to pharmacogenomics and over 300 medications of interest. We limited initial testing to patients with colorectal cancer. Pharmacists provided dosage recommendations based on test results in real-time.
Results:
At our cancer center, 155 patients underwent pharmacogenomics testing from November 2017 to January 2019. Results were available within 3 to 5 days of testing for most patients and were integrated into treatment decision-making. Of 155 sampled participants, a total of 89 (57.4%) participants had an UGT1A1 variant genotype, NM_000463.2: c.-53_-52[8] *1/*28, n = 74 (47.7%); *28/*28, n = 15 (9.7%). Additionally, 4 (2.6%) participants were heterozygous for dihydropyrimidine dehydrogenase. Two (1.3%) individuals were heterozygous for both UDP-glucuronosyltransferase and dihydropyrimidine dehydrogenase genes. All (100%) the patients had at least 1 actionable aberration related to supportive care medications (CYP-family) of all the possible medications listed on their pharmacogenomics report.
Conclusion:
Preemptive comprehensive pharmacogenomics testing can be integrated into clinical practice in real-time for patients with cancer given faster turnaround and low cost. Pharmacist-driven, patient-specific medication management consults add further value given the number of genes/drugs. This sets the stage for a prospective randomized clinical trial to demonstrate the amount of benefit this can result in these patients.
Insights
Pharmacogenomics testing in metastatic colorectal cancer improves patient outcomes by guiding drug selection and dosage. This study shows its feasibility and value in clinical practice for personalized cancer care.
Area of Science:
- Oncology
- Pharmacogenomics
- Clinical Pharmacy
Background:
- Germline pharmacogenomics testing offers a strategy to optimize chemotherapy for metastatic colorectal cancer (mCRC).
- Genes like dihydropyrimidine dehydrogenase (DPD) and UDP-glucuronosyltransferase (UGT) are crucial for metabolizing 5-fluorouracil and irinotecan.
- Previous analyses, such as the TRIBE trial, indicated a link between DPD/UGT aberrations and serious adverse events in mCRC patients.
Purpose of the Study:
- To assess the feasibility and clinical utility of integrating comprehensive pharmacogenomics testing into routine practice for cancer patients.
- To evaluate the impact of real-time pharmacist-led genetic testing interpretation on treatment decisions.
Main Methods:
- Implemented a OneOme RightMed comprehensive pharmacogenomics test covering 27 genes and over 300 medications.
- Focused initial implementation on patients with colorectal cancer.
- Pharmacists provided real-time dosage recommendations based on test results.
Main Results:
- 155 patients underwent testing between November 2017 and January 2019, with results available in 3-5 days.
- A high prevalence of actionable genetic variants was observed: 57.4% had UGT1A1 variants, 2.6% had DPD heterozygosity, and 1.3% had both.
- All patients (100%) possessed at least one actionable pharmacogenomic finding related to supportive care medications (CYP-family).
Conclusions:
- Preemptive, comprehensive pharmacogenomics testing is feasible in clinical practice for cancer patients due to rapid turnaround times and decreasing costs.
- Pharmacist-driven medication management based on genetic data provides significant value.
- These findings support the initiation of prospective trials to quantify the clinical benefits of this approach.
