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- 1. The Clinical Implementation ofPrecision Medicine Lincoln Nadauld, MD PhD Executive Director, Precision Genomics Intermountain Healthcare
- 2. Precision Medicine: AnOverview • Precision medicine overview • Clinical trials in precision oncology • The evidence • The future
- 3. Precision oncology paradigm Variants 1.HER2 2. P53 3. MEK1 4. EGFR 5. FGFR1 Genomic analysis Cancer cell Gene/drug match
- 4. Precision Medicine atNIH nih.gov
- 5. Precision Medicine: Whynow? nih.gov
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- 7. Precision oncology inpractice: we’re already doing it Imatinib in CML Trastuzumab in HER2+ BC Drucker et al., NEJM. 2006 Slamon et al., NEJM. 2001 Survival of CML Patients Gleevec Interferon Chemotherapy months after beginning of treatment Chemotherapy + trastuzumab Chemotherapy Overall survival, %
- 8. Challenges in PrecisionOncology: Tumor Heterogeneity Gerlinger, NEJM, 2012
- 9. Challenges in precisiononcology: Tumor Evolution Puente, Nat. Genet., 2013
- 10. B. Vogelstein, Science.2013 Challenges in Precision Oncology: Mutation Burden
- 11. Precision oncology inspite of the challenges mdanderson.org
- 12. A typical precisiononcology workflow Day 1 Day 2-4 Day 5 Day 6 Day 9-11 Day 12-13 Day 14-15 Molecular Tumor Board Results and Treatment Biopsy or FFPE Pathology Review Sample Prep Day 7-8 Molecular analysis (NGS) Clinic Bioinformatics
- 13. Molecular Tumor Board •Multi-institutionalparticipants •Experts in Cancer Genomics •Interpretation of Genomics
- 14. Precision Medicine: AnOverview • Precision medicine overview • Clinical trials in precision oncology • The evidence • The future
- 15. Precision oncology trialdesigns nih.gov
- 16. Precision oncology trialdesigns nih.gov
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- 18. Precision Medicine: AnOverview • Precision medicine overview • Clinical trials in precision oncology • The evidence • The future
- 19. Precision oncology: Ameta-analysis Schwaederle et al., JCO. 2015
- 20. Improved PFS withPersonalized Medicine Schwaederle et al., JCO. 2015
- 21. Precision Oncology CohortStudy 61 with actionable mutation, and received targeted trx 36 genomics+trg trx match: dx, age, gen, #prev. trx Patients received standard trx within Intermountain 36 standard trx match: dx, age, gen, #prev. trx Assess: -PFS -Cost of care Assess: -PFS -Cost of care 25 without match: dx, age, gen, prev. trx Haslem et al, JOP, 2016
- 22. Precision Oncology Outcomes:Improved survival, decreased costs Haslem, J. Onc. Practice 2016 Progression Free Survival: 23w vs 12w
- 23. Precision Oncology: OverallSurvival Haslem et al., Oncotarget. 2018 ~$30 / week ~$70K / week Standard chemotherapy (n=22) Targeted cancer therapy (n=22) 100 90 80 70 60 50 40 30 20 10 Weeks after treatment start Avg. overall survival = 25.8 wks Healthcare costs Avg. PFS = 11.0 wks Avg. overall survival = 51.7 wks Avg. PFS = 21.4 wks
- 24. Control (N=22) Targeted (N=22) Difference Inpatient $552 $448($104) Outpatient $2,376 $1,167 ($1,209) ER $34 $45 $11 Rx drugs $346 $940 $594 Hospice $146 $9 ($137) Sequencing $0 $112 $112 Total/week $3,453 $2,720 ($734) Precision Oncology Costs Haslem and Nadauld, Oncotarget. 2018
- 25. Precision Medicine: AnOverview • Precision medicine overview • Clinical trials in precision oncology • The evidence • The future
- 26. Precision Health “The visionwould be to go beyond Precision Medicine: instead of a frantic race to cure disease after the fact, we can increasingly focus on preventing disease before it strikes. By focusing on health and wellness, we can also have a meaningful impact in reducing healthcare costs…we call this idea Precision Health.” Minor, L., Forbes Tech. 2016
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- 28. Precision Medicine hasdifferent forms Not all precision medicine initiatives require genomics
- 29. Precision Medicine: Patientreported outcomes improves survival Basch et al., JAMA. 2017
- 30. Intermountain Precision Medicine:moving forward • Biorepository studies and population genomics • Oncology Precision Network (OPeN) • Intermountain Precision Health
- 31. Intermountain Biorepository • 4.5million archival samples • Accumulated from 1975-present • Longitudinal healthcare outcome data (30yrs)
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- 33. GCB-CRC, Genomics ofColon Cancer High depth Whole Genome and RNAseq of T/N samples from 150 patients Cancer type – Stage III colon cancer – Adjuvant chemotherapy – 23% have survival >5yr Genomic endpoints – SNV, rearrangements – CNV (low-depth as pilot project) – Expression, allele specific expression, fusions Analysis – Markers for survival – Landscape of variants – Interactions between variant type 0 5 10 15 20 25 30 35 40 Frequency of Survival (years)
- 34. Overview: Intermountain PrecisionMedicine • Biorepository studies and population genomics • Oncology Precision Network (OPeN) • Intermountain Precision Genomics
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- 36. Anticipated Reach ofOPeN 136,000 New Cancer Cases Per Year 598 Oncologists 241 Hospitals
- 37. Search data byclinical or molecular characteristics
- 38. Overview: Intermountain PrecisionMedicine • Precision medicine cohort study • Biorepository studies and population genomics • Oncology Precision Network (OPeN) • Intermountain Precision Genomics
- 39. Vision: “To becomethe most genetically advanced healthcare system in the world.”
- 40. Goal: Implement Pharmacogenomictesting in the primary care setting Pharmacogenomics
- 41. Goal: Implement inheritedrisk allele testing in primary care
- 42. Goal: Provide genomeservices for internal and external customers Translational Science Center
- 43. Goal: Direct toconsumer genomics
- 44.