Biomarkers Testing In Oncology

Front 1

What is a biomarker

Back 1

It is a biological molecule that may be objectively measyred and evaluated as an indicator of:
1. normal biological process
2. abnormal process
3. pharmacologic response to therapy

Front 2

Classification of cancer biomarkers

Back 2

diagnostic
predictive
prognostic
pharmacodynamic

Front 3

Disease specifc biomarkers can:

Back 3

detect or identify disease
potential effect of the drug on the disease
predict response to treatment
determine likely outcome

Front 4

Definition of personalized medicine

Back 4

refers to tailoring to the individual characteristics of each patient and disease. It involves indentifying subgroups of patients who might benefit from more specific therapies

Front 5

What was the first oncology targeted drug

Back 5

tamoxifen (binding of estrogen receptor)

Front 6

What was the first classification of NSCLC - considered to be the first step in personalized medicine in NSCLC

Back 6

Squamous and nonsquamous subtypes

Front 7

Bev in early development caused bledding compliacitons in which NSCLC sub-type

Back 7

Squamous

Front 8

Which histology showed to be a predictor of improved survival following therapy with premetrexed

Back 8

Nonsquamous (no benefit was observed in patients with squamous histology)

Front 9

Which was the first mutation identified in patients with NSCLC

Back 9

KRAS - year 1987

Front 10

Known mutations identified in NSCLC

Back 10

KRAS, EGFR, EML4-ALK, HER2, BRAF, MET, AKT1, MAP2K1, PI3KCA

Front 11

What is the term "precision medicine"

Back 11

the precise tailoring of diagnostic, prognostic, and therapeutic strategies to the molecular profile of each patient or tumor.

Front 12

What is Reflex testing

Back 12

the automatic testing for specific biomarkers during a diagnostic workup

Front 13

Reflex testing is well established in which tumor types

Back 13

Breast (HER2), colorectal (KRAS codon 12 &13), CML (BCR-ABL translocation)

Front 14

Benefits of reflex testing

Back 14

1. MInimized turnaround time for molecular testing
2. Availability of molecular diagostic results in all patients with adequate biopsy tissue
3. Standardize testing procedures for better consistency
4. Increased efficiency as a result of streamlined testing procedures and coordination among specialists
5. Integration of data about the tumor into one pathology report and the patients medical records

Front 15

EGFR dysregulation has been seen in what % of east Asian patients

Back 15

50% (10% of caucasians)

Front 16

EGFR iknase domain mutations and amplification occur at what % of frequency in East Asian patients

Back 16

40% (15% in caucasians)

Front 17

True or False: Kinase domain mutations are very reare in patients with squamous cell histology

Back 17

True: amplification is seen in 30% of cases and mutations in the extracellular portion of teh receptor in 5% of cases

Front 18

List the 2 most frequent EGFR mutations that when activated serve as predictive biomarkers for positive response to EGFR inhibitors

Back 18

E746-A750 deletion - 44%
L858R point deletion - 41%

Front 19

What % of patients with NSCLC carry EML4-ALK rearrangements (mutations) and what ALK inhibitor is approved to treat these patients?

Back 19

4-7%, crisotinib (Xalkori)

Front 20

List some important facts associated iwth KRAS mutations

Back 20

1. occurs in 15-20% of pts with NSCLC, and in 30%-50% of pts with adenocarcinoma histology
2. Rarely occurs in squamous cell pts
3. Usually exclusive to EGFR mutations
4. Usually occurs early in the development of smoking related adenocarcinoma

Front 21

List physicians who perform biopsies

Back 21

Pulmonologists (bronchoscope)
Interventional radiologists (CT)
thoracic surgeons (surgery)

Front 22

Describe the steps associated with the biomarker testing flow

Back 22

1. request tumor biopsy
2. biopsy procedure
3. pathologist identifies histologic subtype and tissue quality. If the tissue sample contains non-squamous cell components, the pathologist also identifies a sample that is appropriate for molecular testing
4. Molecular testing done
5. results sent for treatment decision

Front 23

Which are the groups that currently have biomarker testing guidelines in place in NSCLC

Back 23

NCCN
ASCO
CAP
IASLC
AMP

Front 24

Describe the NCCN biomarker testing guidelines for NSCLC

Back 24

Recommend EGFR and ALK testing in patients with metastaic or recurrent disease and confirmed non-squamous cell histology (EGFR and ALK testing not routinely recommended for patients with squamous histology)

Front 25

Describe the CAP/IASLC/AMP draft biomarker testing guidelines for NSCLC

Back 25

1. EGFR and ALK testing on all NSCLC patients with adenocarcinoma regardless of histologic grade/subtype
2. Patients with stage 3/4 should be tested at the time of Dx. Decision for patients with stage 1/2 disease should be made by each institution/provider
3. Sequential testing algorithms should be in place. EGFR first followed by ALK fish

Front 26

Describe the ASCO biomarker testing guidelines for NSCLC

Back 26

Based on 5 randomized controlled studies, patients with advanced NSCLC who are being considered for EGFR therapy (TKI) not previousley treated with a TKI should be tested for 1st line therapy

Front 27

What is considered to be the best method to obtain tissue in patietns with MET NSCLC

Back 27

CT-guided core needle biopsy

Front 28

After CT guided core needle biopsy, other methods that are preferred are

Back 28

EBUS-NA, CT guided FNA, thoracentesis and bronchoscopy

Front 29

What is a PMA application?

Back 29

It is an application to request to market or continue marketing, a class 3 product. FDA needs to ensure that the product is safe and effective

Front 30

What is a class III (3) product

Back 30

Product that falls under the most stringent FDA regulatory approval process. This class includes products or devices that sustain life, contribute to the precention of impairment of human health or pose a risk of illness or injury

Front 31

What is a 510(k) FDA premarketng submission

Back 31

For products that are substantially equivalent to already marketed products that are not subject to PMA

Front 32

What is BATTLE

Back 32

Stands for Biomarker Integrated Approaches of Targeted Therapy for Lung Cancer Elimination - a propespective clinical trial (phase 2) aimed to indentify tumor response and help select personalized therapy for patients with NSCLC. Patients were enrolled into 1 of 4 arms based on molecular testing results for 11 biomarkers, including EGFR, KRAS and BRAF. Study demonstrated potential improved outcomes

Front 33

Name the several randomized, well controlled phase 3 trials for patiens with NSCLC with confirmed EGFR mutations through biomarker testing

Back 33

*IPASS: Gefi vs. Carbo+Pac
*IPASS EGFR mutation analysis: Gefi 9.6 vs. carbo+Pac 6.3 months PFS
*WJTOG3405: Gefi 9.2 vs. cis+doce 6.3 months PFS
*NEJSG: Gefi 10.8 vs. carbo+pac 5.4 months PFS
*OPTIMAL: Erlo 10.8 vs. carbo+pac months 5.4 PFS
*EURTAC: Erlo 9.4 vs. chemo 5.2 PFS months

Front 34

CLIA

Back 34

CLinical Laboratory Improvement Amendments - established by Congress in 1988 with the goal of establishing standards in lab testing

Front 35

List acceptable methods/diagnostic techniques for detecting EGFR mutations for the purpose of therapy selection

Back 35

Sanger sequencing
ARMS
PCR
Fragment length analysis
dHPLC