Personalized Oncology - IntermountainPhysician · 2015-11-19 · Personalized Oncology Derrick...
Transcript of Personalized Oncology - IntermountainPhysician · 2015-11-19 · Personalized Oncology Derrick...
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Cancer Genomics Personalized Oncology
Derrick Haslem, MD Intermountain Southwest
Cancer Center Intermountain Precision
Genomics
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Intermountain Southwest Cancer Services
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Cancer Experience
Grow into a “tumor” or “neoplasm” Cancer cells spread from there to lymph
nodes and other organs Cancer cells that spread still have same
characteristics of cell of origin • Same properties and characteristics
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Staging: Local, Regional, Metastatic
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Goals of treatment vary by stage
Local/Regional • Curative treatment
strategy • Treat micro-
metastasis
Metastatic • Palliative treatment
strategy • Buy “quality” time
Treatment options • Surgery • Radiation • Chemotherapy • Targeted therapies
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History of Chemotherapy
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Chemotherapy
Goal is to reduce cancer burden
Affects ALL cells Since cancer cells
divide rapidly, they are typically more affected
Through trial and error, chemotherapy progressed
Outcome measured: Did patients live longer?
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Side Effects of Chemo
Chemo acts on actively dividing cells
Predictable side effects • Nausea • Hair loss • Low blood
counts
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Traditional Chemotherapy
• Chemotherapy is not effective in every case
• Non-targeted, toxic resulting in expected side effects
• Large selection of drugs with a low response rate. § Results in high variation, inefficiencies and
increased costs
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Cancer Hallmarks Unregulated growth Insensitive to anti-growth
signals Evades apoptosis Multiply indefinitely Stimulate angiogenesis Activation of metastasis and
invasion of tissue
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The Human Genome
46 chromosomes
20,000 genes
1 Human Genome
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Normal and Aberrant Genes
insu
lin
albu
min
grow
die
KRAS P53* *
grow grow grow
die die die
x
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Genome Aberrations
Faulty Genes
1. FGFR1
2. P53
3. MEK1
4. EGFR
5. HER2
Genomic analysis
Cancerous cell
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B. Vogelstein, Science. 2013
Number of Mutations in Human Cancers
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Precision Genomics Cancer Therapy
mdanderson.org
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Clinical Cancer Genomics Program
• Personalized Medicine Clinic
• Genomic Testing
• Molecular Tumor Board
• Drug Procurement
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Cancer Genomics Workflow
Day 1
Day 2-5
Day 6
Day 7-8
Day 12-13
Day 13-14
Day 14-18
Molecular Tumor Board
Results and Treatment
Tumor Biopsy or FFPE
Pathology Review
Sample Prep
Analytics
Day 9-11 Molecular
analysis (NGS)
Personalized Medicine Clinic
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Molecular Tumor Board
• Multi-institutional participants
• Experts in Cancer Genomics
• Interpretation of Genomics
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E-portal for ordering/results delivery:
www.precisioncancer.org
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Genomic Testing: Impact on Management
n= 195
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Intermountain Precision Medicine Cohort Study
195 assessed for eligibility (had genomic testing)
154 with actionable mutation
75 with actionable mutation,and received targeted trx
36 precision trx match: dx, age, gen,
#prev. trx
Patients received standard trx within Intermountain
36 standard trxmatch: dx, age, gen,
#prev. trx
Assess:-PFS
-Cost of care
Assess:-PFS
-Cost of care
41 without actionable mutation
79 did not received precision trx
39 without match:dx, age, gen, prev. trx
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Baseline Characteristics
Targeted ControlCharacteristic No. % No. %Meanage,years 67.8 67Gender
male 22 61.1 22 61.1female 14 38.9 14 38.9
RaceWhite 36 100 30 83.3Black 0 0 1 2.8
Hispanic 0 0 4 11.1Other 0 0 1 2.8
LineofTreatment1stline 0 0 1 2.82ndline 19 52.8 19 52.83rdline 9 25 8 22.24thline 1 2.8 3 8.35thline 2 5.6 1 2.86thline 4 11.1 3 8.37thline 1 2.8 1 2.8Mean 3.1 2.9
TypeofCancerBladder 2 5.6 2 5.6Breast 5 13.9 5 13.9
Cholangio 1 2.8 1 2.8Colon 8 22.2 8 22.2Gastric 1 2.8 1 2.8
HeadandNeck 4 11.1 4 11.1Lung 11 30.6 11 30.6
Melanoma 1 2.8 1 2.8Ovary 1 2.8 1 2.8
Pancreas 2 5.6 2 5.6
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Diverse Tumor Types
n n % %
Control Targeted
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Primary Outcome: Progression Free Survival
36 precision trx match: dx, age, gen,
#prev. trx
36 standard trxmatch: dx, age, gen,
#prev. trx
Assess:-PFS
-Cost of care
Assess:-PFS
-Cost of care
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Clinical Trial: Traditional vs Targeted
Progression Free Survival: Traditional: 12.0 weeks Targeted: 22.9 weeks
HR: 0.53, p<0.002
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Progression Free Survival
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Secondary Outcome: Cost of Care
Cost of Care:
Standard: $5,011/wk Precision Med: $4,682/wk
p= 0.22
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Patient examples
46 female with metastatic melanoma Spread to brain, adrenal glands Not responding to standard treatments
Genomic analysis of the tumor was performed Revealed a KIT mutation
Started Imatinib Safe, oral, well-tolerated drug for CML
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…after 2 months of imatinib
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Patient Case: Colon Cancer
40s yo man with metastatic colon cancer Progressed through multiple treatments Genomic analysis: HER2 amplification
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Patient Case: Colon Cancer (cont’d)
Ø 3 months of drug, tumor shrinking (13 month improvement)
Ø he and his 3 children are thrilled
Chemo TDM-1 2 dosesChemo
TDM-1 3 doses
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Patient Case: Lung Cancer
• 79 year old man with metastatic lung cancer (lung)
• Progressed through carbo/gemcitabine, docetaxel
• Genomic analysis: FGFR1 amplification
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Patient Case: Lung Cancer
Targeted trx, 3 mo Targeted trx, 6 moChemo
Pt now on treatment >14 months, an oral pill • He reports feeling “very optimistic about life.”
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Cancer Genomics is NOT:
NOT a cure May turn it into a chronic disease; ie CML
NOT used to figure out Family Relations Genomic evaluation on the tumor NOT the patient
NOT applicable to every patient/cancer Case by case basis; although changing
NOT guaranteed to work It is new and bugs are still being worked out
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Cancer Genomics IS: More options for patients with incurable disease Progress towards a cure or turning cancer into a
chronic disease Exciting technology with clinical application
Opportunity to make life better for patients