1. Clinical Implementation of Genomic Cancer Medicine
Lincoln Nadauld MD, PhD Director, Cancer Genomics Intermountain Healthcare
Consulting Assistant Professor
Stanford University, School of Medicine

2. High Jump Standard: Scissor Kick

3. Innovation: Fosbury Flop

4. What does Dick Fosbury have to do with Genomic Cancer Medicine?

5. INNOVATION

6. Overview What is Genomic Cancer Medicine? (case study)
Intermountain Clinical Cancer Genomics Program
Outcomes
Future Vision and Next Steps

8. Clinical Case, continued
2009
Advanced disease (L ovary)
Surgery and radiation
Genomic analysis of tumor

9. An unexpected gene mutation
FGFR2
10p
10q
Nadauld et al., Genome Biology. 2014

10. A drug for FGFR2! =

11. What is Genomic Cancer Medicine? (a primer)

12. The Human Genome
1 Human Genome
46 chromosomes
20,000 genes

13. Normal and Aberrant Genes
insulin
albumin
grow
die *
grow
die x
KRAS
P53

14. Number of Mutations in Human Cancers
B. Vogelstein, Science. 2013

15. Genome Aberrations Faulty Genes FGFR1 P53 MEK1 EGFR HER2
*drug 1*
*drug 2*
*drug 3*
Genomic analysis
*drug 4*
Cancerous cell

16. Genomic Targets
ccr.cancer.gov

17. Could Genomic Cancer Medicine Add Value?

18. Value in Healthcare =
Quality-adjusted outcome
Cost
Value

19. Build a Model!

20. Overview What is Genomic Cancer Medicine?
Intermountain Clinical Cancer Genomics Program
Outcomes
Future Vision and Next Steps

21. Clinical Cancer Genomics Program
Genomic Testing
Personalized Medicine Clinic
Molecular Tumor Board
Treatment delivery

22. Cancer Genomics Workflow
Molecular analysis (NGS)
Personalized Medicine Clinic
Day 8-9
Day 1
Day 10-12
Tumor Biopsy or FFPE
Analytics
Day 2-3
Molecular Tumor Board
Day 13
Pathology Review
Day 4-5
Sample Prep
Results and Treatment
Day 6-7
Day 14

23. Molecular Tumor Board Multi-institutional participants
Experts in Cancer Genomics
Interpretation of Genomic Findings

24. Intermountain Cancer Genomics

25. Overview What is Genomic Cancer Medicine?
Intermountain Clinical Cancer Genomics Program
Outcomes
Future Vision and Next Steps

26. Patient Case: Colon Cancer
40s yo man with metastatic colon cancer Progressed through multiple treatments Genomic analysis: HER2 amplification

27. Patient Case: Colon Cancer (cont’d)
Targeted drug
2 doses
Targeted drug
3 doses
Chemo
Chemo
he and his 5 children are thrilled

28. Patient Case: Lung Cancer
56 year old man with metastatic lung cancer
Progressed through standard chemotherapy regimen
Genomic analysis: BRAF mutation

29. Patient Case: Lung Cancer (cont’d)
Targeted treatment x 9months
Before
After

30. Patient Case: Melanoma
52 year old woman with metastatic melanoma
Progressed through standard treatment
Genomic analysis: cKIT alteration

31. Patient Case: Melanoma
8 months on targeted therapy for c-kit mutation:

32. Patient Case: Lung Cancer
79 year old man with metastatic lung cancer (lung)
Progressed through carbo/gemcitabine, docetaxel
Genomic analysis: FGFR1 amplification

33. Patient Case: Lung Cancer
Chemo
Targeted, 3 mo
Targeted, 6 mo
Pt now on treatment >20 months, an oral pill
He reports feeling “very optimistic about life.”

34. Genomic Testing: Impact on Management

35. Genomic Medicine Stats
Actionable Mutations and Targeted Therapy
No. of patients (percent)
Genomic diagnostic performed
210
Adequate Tissue available or re-biopsied
195
No. of mutations
4 (2%) 1
19 (10%) 2
23 (12%) 3
37 (19%)
>3
111 (57%)
No. of actionable mutations
156
No. of patients with actionable mutation
132 (68%)
No. of pts with actionable gene and received targeted tx
99 (51%)

36. Summary New technologies are changing medicine now
Data to support the use of new tech is accumulating
Genomic cancer medicine appears to yield superior outcomes

37. Next Steps—Cancer Genomics
Monitor Outcomes
Publish outcomes and cost data
Make Cancer Genomics broadly available (precisioncancer.org)
Conduct Randomized Prospective Trial

38. Future Vision Multi-disciplinary Genomics
Cardiovascular genomics (high risk patients)
Neonatal genomics (hyperbilirubinemia)
Neurosciences (alzheimer’s, ALS, Autism)
Infectious Disease (rare infections)

39. Acknowledgements CPHCC Intermountain Leadership
Cancer Clinical Program
NIH/National Cancer Institute
Stanford University
Stanford Genome Tech Center
U of Oklahoma
Sypase