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
http://www.mychances.net/images/college/1416-crest-250-200-69f66bc4e09bf96305a6c6516f183c63.pnghttp://www.mychances.net/images/college/1416-crest-250-200-69f66bc4e09bf96305a6c6516f183c63.png
Hertz and McLeod, Clin Pharm Ther (2016)
Precision Medicine for Cancer Treatment
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)
Oncologists are Primed for PGx Use
Bonter et al., BMJ Open (2011)
Mercaptopurine Pharmacogenetics (II)
• Intermediate Activity Patients: dose at 30-80% of normal
• Deficient Patients: drastically reduce dose and frequency
Relling et al., CPT (2011)
Genotype-Directed Dosing of Irinotecan
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)
5-Fluorouracil and DPD Deficiency
Cancer Prospective Testing
Deenen et al. JCO (2016)
Genotype-Directed Dosing
Deenen et al. JCO (2016)
*Net savings to the institution with preemptive screening
($3,767/patient; $3,828/pt for nonscreening)
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.”
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?
Hypothesis
Providing preemptively-obtained pharmacogenomic results at the time of
prescribing will improve prescribing decisions, and patient outcomes
“Genomic
Prescribing
System” (GPS)
from Ratain CPT 2007
Model
BROAD CUSTOM TEST PANEL
(all relevant genotypes assayed)
PREEMPTIVE TESTING
(not reactive)
BUNDLED, “LIFETIME” TEST
(reduces marginal cost)
PATIENT and PROVIDER
ENGAGEMENT
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
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)
Patient Perceptions of Personalized Care
Physician Accessed GPS: OR 1.8 [95% CI 1.2-2.9], P
*p=0.001
Borden et al., Pharmacogenomics J, 2019
Could Pharmacogenomic-Guided Prescribing Improve Medication Adherence?
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
Future Directions
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
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