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Pharmacogenomics Implementation for Oncology
Peter H. O’Donnell, M.D.
Department of Medicine
Committee on Clinical Pharmacology and Pharmacogenomics
Center for Personalized Therapeutics
The University of Chicago
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Hertz and McLeod, Clin Pharm Ther (2016)
Precision Medicine for Cancer Treatment
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Pharmacogenomics (PGx)
• Study of the effect of genetic variation on drug response or toxicity
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Germline Pharmacogenomics Are We Ready?
• Survey of >10,000 U.S. physicians:
– 98% believe genetic profiles may influence drug therapy
– 13% had ordered a pharmacogenomic (PGx) test
– 10% feel adequately informed about PGx testing
Stanek et al., CPT (2012)
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Oncologists are Primed for PGx Use
Bonter et al., BMJ Open (2011)
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Mercaptopurine Pharmacogenetics (II)
• Intermediate Activity Patients: dose at 30-80% of normal
• Deficient Patients: drastically reduce dose and frequency
Relling et al., CPT (2011)
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Genotype-Directed Dosing of Irinotecan
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A Very Recent Example - Abiraterone
Hahn et al. Mol Cancer Ther (2019)
SLCO2B1 encodes a
transporter for
steroids including
abiraterone into cells
(AG = 18.5% of
population)
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5-Fluorouracil and DPD Deficiency
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Cancer Prospective Testing
Deenen et al. JCO (2016)
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Genotype-Directed Dosing
Deenen et al. JCO (2016)
*Net savings to the institution with preemptive screening
($3,767/patient; $3,828/pt for nonscreening)
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8% of patients carried one of these variantsLancet Oncology (2018)
“Since fluoropyrimidines are among the most
commonly used anticancer agents, these findings
suggest that implementation of DPYD genotype-
guided individualized dosing should be a new
standard of care.”
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Barriers to Realizing Pharmacogenomic Implementation
• PGx test availability
• Delay in obtaining results
• Lack of provider knowledge
• Evolving PGx evidence base
• Provider concerns regarding interpretation
• Who Pays?
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Hypothesis
Providing preemptively-obtained pharmacogenomic results at the time of
prescribing will improve prescribing decisions, and patient outcomes
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“Genomic
Prescribing
System” (GPS)
from Ratain CPT 2007
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Model
BROAD CUSTOM TEST PANEL
(all relevant genotypes assayed)
PREEMPTIVE TESTING
(not reactive)
BUNDLED, “LIFETIME” TEST
(reduces marginal cost)
PATIENT and PROVIDER
ENGAGEMENT
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Current GPS Content• Reportable information for:
70
Medications
>100
Germline
Variants
>50
Genes
• Oncology Drugs with Germline PGx:
capecitabine/fluorouracil, doxorubicin, irinotecan,
mercaptopurine, tamoxifen, vincristine, cisplatin,
ondansetron, codeine, tramadol, oxycodone
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Pharmacogenomics Alters Drug Prescribing
No pharmacogenomically high-risk medications were prescribed during the entire
study when physicians consulted the GPS toolO’Donnell et al., Clin Pharm Ther (2017)
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Patient Perceptions of Personalized Care
Physician Accessed GPS: OR 1.8 [95% CI 1.2-2.9], P
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*p=0.001
Borden et al., Pharmacogenomics J, 2019
Could Pharmacogenomic-Guided Prescribing Improve Medication Adherence?
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Conclusions
• Successfully implemented an individualized health care model of preemptive pharmacogenomic testing
• Patient interest robust; physician adoption high
• Pharmacogenomic information improved prescribing in a pattern aimed at reducing patient risk
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Future Directions
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Acknowledgements
NIH 1R01HG009938-01A1
NIH 1U54MD010723-01
Bucksbaum Institute Associate Faculty Scholar Pilot Grant
Chicago Innovation Exchange - Innovation Fund Award
The University of Chicago Cancer Research Foundation Auxiliary
The William F. O’Connor Foundation
Central Society for Clinical and Translational Research