Cancer Genomics Personalized Oncology

Derrick Haslem, MD Intermountain Southwest

Cancer Center Intermountain Precision

Genomics

Intermountain Southwest Cancer Services

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

Staging: Local, Regional, Metastatic

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

History of Chemotherapy

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?

Side Effects of Chemo

Chemo acts on actively dividing cells

Predictable side effects •  Nausea •  Hair loss •  Low blood

counts

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

Cancer Hallmarks Unregulated growth Insensitive to anti-growth

signals Evades apoptosis Multiply indefinitely Stimulate angiogenesis Activation of metastasis and

invasion of tissue

The Human Genome

46 chromosomes

20,000 genes

1 Human Genome

Normal and Aberrant Genes

insu

lin

albu

min

grow

die

KRAS P53* *

grow grow grow

die die die

x

Genome Aberrations

Faulty Genes

1.  FGFR1

2.  P53

3.  MEK1

4.  EGFR

5.  HER2

Genomic analysis

Cancerous cell

B. Vogelstein, Science. 2013

Number of Mutations in Human Cancers

Precision Genomics Cancer Therapy

mdanderson.org

Clinical Cancer Genomics Program

• Personalized Medicine Clinic

• Genomic Testing

• Molecular Tumor Board

• Drug Procurement

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

Molecular Tumor Board

• Multi-institutional participants

• Experts in Cancer Genomics

• Interpretation of Genomics

E-portal for ordering/results delivery:

www.precisioncancer.org

Genomic Testing: Impact on Management

n= 195

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

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

Diverse Tumor Types

n n % %

Control Targeted

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

Clinical Trial: Traditional vs Targeted

Progression Free Survival: Traditional: 12.0 weeks Targeted: 22.9 weeks

HR: 0.53, p<0.002

Progression Free Survival

Secondary Outcome: Cost of Care

Cost of Care:

Standard: $5,011/wk Precision Med: $4,682/wk

p= 0.22

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

…after 2 months of imatinib

Patient Case: Colon Cancer

40s yo man with metastatic colon cancer Progressed through multiple treatments Genomic analysis: HER2 amplification

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

Patient Case: Lung Cancer

• 79 year old man with metastatic lung cancer (lung)

• Progressed through carbo/gemcitabine, docetaxel

• Genomic analysis: FGFR1 amplification

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.”

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

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