Biomarkers and Biomarker Testing

Question 1

What are the Guideline Sources for Biomarker Testing?

Hint: CAN

Answer 1

College of American Pathologists/Intl. Assc. for the Study of Lung Cancer/Assc. for Molecular Pathology (CAP/IASLC/AMP)

American Society of Clinical Oncology (ASCO)

National Comprehensive Cancer Network (NCCN)

Question 2

What is a Diagnostic Biomarker?

Answer 2

Biomarker used to detect or confirm presence of a disease or condition of interest or to identify individuals with a subtype of the disease

Is there an illness? What type of disease is it?

Question 3

What is a Monitoring Biomarker?

Answer 3

Biomarker measured serially for assessing status of a disease or medical condition or for evidence of exposure to (or effect of) a medical product or an environmental agent

What is the status or extent of a disease or medical condition?

Question 4

What is a Predictive Biomarker?

Answer 4

Biomarker used to identify individuals who are more likely than similar individuals without the biomarker to experience a favorable or unfavorable effect from exposure to a medical product or an environmental agent

What is the likelihood of response to a treatment?

Question 5

What is a Prognostic Biomarker?

Answer 5

Biomarker used to identify likelihood of a clinical event, disease recurrence, or progression in patients who have the disease or medical condition of interest

What is the likelihood of a particular clinical outcome?

Question 6

What is the difference between an Actionable Biomarker and an Emerging Biomarker?

Answer 6

Actionable biomarkers can be targeted by FDA approved products whereas products targeting emerging biomarkers are still under investigation

Question 7

Actionable Biomarker(s) for Targeted Therapy with TKIs?

Hint: RAMEN-R

Answer 7

RET
ALK
MET
EGFR
NTRK
-
ROS1

Question 8

Actionable Biomarker(s) for Combined BRAF and MEK Inhibitors?

Answer 8

BRAF

Question 9

Actionable Biomarker(s) for Immune Checkpoint Inhibitors?

Answer 9

PD-L1 Expression Levels (immune checkpoint protein that inhibits T-cell activation)

Question 10

Emerging Biomarker(s) for NSCLC?

HINT: TEK

Answer 10

TMB
ERBB2 (HER2)
KRAS

Question 11

True or False; the presence of a known activating mutation in KRAS identifies patients who are unlikely to benefit from further molecular testing?

Answer 11

True

Question 12

What is the incidence of KRAS mutations in NSCLC patients?

Answer 12

25 - 35%

Question 13

True or False; NCCN, CAP/IASLC/AMP, and ASCO recommend expanded testing of KRAS as an emerging biomarker

Answer 13

True

Question 14

True or False; Adhering to guideline-recommended biomarker testing improves outcomes

Answer 14

True

11% decreased risk for all -cause mortality

22% decreased risk for all-cause mortality at 1 year for those with Stage IV initial diagnosis

8% increase in median OS

Question 15

True or False; Many patients do not receive biomarker testing and targeted therapy

Hint: Academic and Government vs. Community

Answer 15

True; only 22% of patients are tested for all four guideline-recommended actionable biomarkers in community practices and 55% of patients with actionable mutations do not receive targeted therapy

Question 16

What are the four guideline-recommended actionable biomarkers?

Hint: BEAR

Answer 16

BRAF
EGFR
ALK
ROS1

Question 17

What are the seven biomarkers recommended by NCCN guidelines?

Hint BEAR REM

Answer 17

BRAF
EGFR
ALK
ROS1

MET
ERBB2
RET

Note: KRAS is not on this list

Question 18

Name five biopsy methods

Answer 18

Sputum cytology, thoracentesis, needle biopsy, bronchoscopy, surgery

Question 19

Under what situations does the NCCN recommend the use of a liquid biopsy?

Hint: Two

Answer 19

1. The patient is not medically fit for invasive tissue sampling
2. The is insufficient tissue for molecular analysis and follow-up tissue-based analysis will be done if a genetic abnormality is not identified by liquid biopsy

Question 20

Name some of the Pros and Cons of Liquid Biopsy

Hint: Consider Method, Tumor Heterogeneity, Sample Collection, Sample Requirements, Sample Integrity

Answer 20

Pros: Minimally invasive blood sample, captures tumor heterogeneity

Cons: Helps when insufficient tissue is available or when patient is unfit for biopsy, not all tumors shed cfDNA, requires fast turnaround to maintain sample integrity

Question 21

Name some of the Pros and Cons of Tissue Biopsy

Hint: Consider Method, Tumor Heterogeneity, Sample Collection, Sample Requirements, Sample Integrity

Answer 21

Pros: Tissue comes directly from the primary tumor or metastatic sites (Gold Standard)

Cons: Collecting adequate sample size, invasive with possible complications (esp. if tumor is inaccessible)

Question 22

True or False; Tissue and liquid biopsy have reasonable concordance (agreement or consistency) across multiple biomarkers?

Answer 22

True

Question 23

Name five methodologies used to assess NSCLC biomarkers

Hint: SNIP-F

Answer 23

Sanger sequencing
NGS
Immunohistochemistry (IHC)
PCR
-
Flourescence in situ hybridization (FISH)

Question 24

Immunohistochemistry (IHC) can detect ___ biomarker(s) at a time and (can / cannot) be used to assess for a KRAS mutation.

Answer 24

One

Cannot

Question 25

Flourescence in situ hybridation (FISH) can detect ___ biomarker(s) at a time and (can / cannot) be used to assess for a KRAS mutation.

Answer 25

One Cannot

Question 26

PCR can detect ___ biomarker(s) at a time and (can / cannot) be used to assess for a KRAS mutation.

Answer 26

One; exception is multiplex PCR Can

Question 27

Sanger sequencing (can / cannot) be used for a KRAS mutation but requires ___% tumor cells to get accurate results.

Answer 27

Can 25 - 30%

Question 28

NGS (does / does not) require selection of biomarkers of interest prior to testing and (can / cannot) be used to assess for a KRAS mutation.

Answer 28

Does not Can

Question 29

True or False; molecular tests (Sanger sequencing, NGS, PCR) can be used to assess for a KRAS mutation

Answer 29

True

Question 30

Which of the following test(s) go through clinical trials for FDA approval to receive indications for specific therapies? ``` Lab-developed test (LDT) Companion Diagnostic (CDx) ```

Answer 30

Companion Diagnostic (CDx); may have a higher standard for analytical and clinical validity due to FDA regulation

Question 31

True or False; there are a few CDx tests approved to test for KRAS in patients with NSCLC

Answer 31

False; however, some CDx's are approved for KRAS testing in colorectal samples to include KRAS G12C.

Question 32

Identify five formats for reporting of KRAS G12C results on a biomarker testing results form

Answer 32

``` Codon: 12 Exon: 2 Amino acid: NP_203524.1; pGly12Cys Nucleotide change: GGT -> TGT; c.34G>T Variant ID: COSM516 ```

Question 33

Which one of the following describes KRAS in its active state and which one describes KRAS in its inactive state. KRAS G12C - GDP KRAS G12C - GTP

Answer 33

GDP - Inactive GTP - Active Hint: Phosphorylation "activates" so tri-phosphate is active, and di-phosphate is inactive

Question 34

KRAS G12C accounts for nearly ___ of all KRAS mutations, making it one of the most prevalent drivers of mutations in NSCLC

Answer 34

Half, or 44%

Question 35

What is a truncal mutation? Hint: Trunk

Answer 35

Mutation that is theoretically present in every cancer cell, or at the trunk of the cancer evolutionary tree

Question 36

True or False; KRAS mutations occur in smokers (current and former) as well as non-smokers

Answer 36

True

Question 37

True or False; KRAS G12C is mutually exclusive from other actionable and emerging mutations and patient status does not seem to change over time

Answer 37

True

Question 38

Which payer type does not require Prior Authorization and no Patient Cost-Sharing? Original Medicare Medicare Advantage Commercial

Answer 38

Original Medicare; but patients may be responsible for an office visit co-pay