Advanced NSCLC Biomarker Testing for KRAS G12C

Who to test

Consider testing for KRAS G12C in eligible patients with NSCLC at diagnosis

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    While the KRAS G12C mutation is most commonly found in smokers, it can occur regardless of clinical or demographic characteristics8

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    Guidelines recommend testing for actionable biomarkers (including KRAS G12C) in patients with advanced NSCLC9

Percentage of patients tested for all
actionable NSCLC biomarkers (2017–2019)10

Less than 1/3 of adult patients with advanced NSCLC received biomarker testing for all actionable biomarkers in the community setting. Additionally, those with a smoking history and who are racial minorities also have a lower chance of getting tested10-12

Why to test

The NSCLC landscape is evolving—check your biomarker panel for actionable biomarkers like KRAS G12C9

  • CAP/IASLC/AMP Guidelines also state that single-gene KRAS testing may be offered in addition to EGFR, ALK, and ROS1, to exclude patients from further testing3

*Includes patients with advanced/metastatic NSCLC, but not locally advanced NSCLC.2

It is recommended at this time that when feasible, molecular testing be performed via a broad, panel-based approach, most typically performed by NGS.2

The NCCN Guidelines® for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.2

Guidelines recognize the value of knowing KRAS G12C status in advanced NSCLC2-4


*It is recommended at this time that when feasible, testing be performed via a broad, panel-based approach, most typically performed by NGS.2
The NCCN Guidelines® for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays.2
Includes patients with advanced/metastatic NSCLC, but not locally advanced NSCLC.2

Consider comprehensive genomic profiling at diagnosis to identify actionable biomarkers like KRAS G12C

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    Conserve tissue

    A broad panel uses less tissue than a series of single-gene tests, so additional tests can be run if needed9

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    Broad panel testing can be cost-effective based on the number of biomarkers requiring testing in NSCLC and may avoid the added cost and risk of rebiopsy13

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    Shorter turnaround time

    Expanded-panel testing at diagnosis may take less time than consecutive single-gene tests in a process-of-elimination approach13

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    Consistent reporting

    Expanded panel testing provides results for many biomarkers in one report rather than multiple different reports14

  • KRAS G12C is already included in most NGS panels and can also be detected by currently available PCR and Sanger sequencing methods5

How to test and report

The KRAS G12C point mutation can be detected in tissue and liquid biopsy specimens using common molecular testing methods5,15

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    Most NGS platforms already test for KRAS G12C. There are also many PCR platforms capable of KRAS G12C testing5

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    Tissue biopsy in NSCLC remains the gold standard—and liquid biopsy shows a high degree of concordance15

  NGS (FFPE sample) PCR (FFPE sample)
Reliability* 1%–10% sensitivity, 95%–100% specificity9,16 1%–5% sensitivity, 96%–100% specificity17-19
DNA/RNA Input 10–1,000 ng DNA/10–200 ng RNA16,20-22 50–300 ng DNA/50–1,000 ng RNA18,20,23,24
Turnaround Time3,9,19,20 4–14 days 1–7 days
  • Specialty infrastructure required25
  • Variable sensitivity and specificity across assays9
  • CAP/IASLC/AMP Guidelines state that single-gene KRAS testing may be offered in addition to EGFR, ALK, and ROS1, to exclude patients from further testing3
    • Consider listing KRAS G12C at the variant level in your reports, as some analytical reports may not specify this mutation7

*Includes whole genome and targeted NGS analyses and quantitative/real-time and digital PCR analyses.9

CAP/IASLC/AMP Guidelines recommend a turnaround time of no more than 10 days.3

Liquid biopsy may be used with high degrees of concordance as an alternative to tissue-based testing15

biopsy-desk biopsy-mob

Image reproduced with permission from Pantel K, et al.26

One form of liquid biopsy consists of obtaining ctDNA from plasma, which can be used to identify genomic alterations26

  • Plasma from blood samples contains circulating cfDNA released from healthy cells and tumor cells
  • Tumor cells release cfDNA known as ctDNA

Liquid biopsy allows for detection of biomarkers when tissue is not available27

  • Up to 25% of patients are ineligible for rebiopsy. If tissue biopsy isn’t an option for your patient, liquid biopsy may be an alternative28
cfDNA vs tissue-based testing for KRAS mutations in patients with mNSCLC15,*
cfDNA_vs_Tissue_Chart  cfDNA_vs_Tissue_Chart 
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    NSCLC liquid biopsy options exist29,30

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    • Consensus statement from IASLC recommends liquid biopsy to replace or complement tissue analysis, depending on the clinical scenario31,*
    • Plasma ctDNA may be used for newly diagnosed patients; results are often complementary to tissue analysis27
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    Utilizing cfDNA in addition to tissue increased the number of patients identified to have a driver mutation by 48%, and patients were significantly more likely to receive the complete genotyping that is recommended by guidelines15,‡

    • If liquid biopsy results are negative, perform a tissue test when feasible as the presence of driver mutations cannot be ruled out from a liquid biopsy sample alone32

*Concordance and PPV for the other guideline-recommended biomarkers was similarly high.15
The number of patients identified to have a driver mutation increased from 60 to 89, including those with negative, not assessed, or insufficient tissue results.15
The guideline-recommended biomarkers in this study included: EGFR, ALK, ROS1, BRAF, RET, METex14 skipping, MET amplification, and ERBB2 (HER2). The number of patients who received complete genotyping increased from 51 to 268 (P < 0.0001).15

Comparing tissue and liquid biopsy testing

*FDA-approved targeted therapies included EGFR, ALK, ROS1, and BRAF.15

Where to test

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    Check with your current pathologist or lab to confirm KRAS G12C is already included in their panel for NSCLC. However, if testing needs to be sent out, see below for a list of some national reference labs that offer testing for KRAS G12C

Lab Location Website Phone Number
ARUP LaboratoriesARUP Laboratories
Salt Lake City, UT
Salt Lake City, UT (800) 522-2787
San Diego, CA
San Diego, CA (888) 332-7729
Boulder, CO
Boulder, CO (303) 417-0500
Caris Life SciencesCaris Life Sciences
Phoenix, AZ
Phoenix, AZ (888) 979-8669
Circulogene TheranosticsCirculogene Theranostics
Birmingham, AL
Birmingham, AL (855) 614-7083
Foundation MedicineFoundation Medicine
Cambridge, MA
Cambridge, MA (888) 988-3639
GenPath DiagnosticsGenPath Diagnostics
Elmwood Park, NJ
Elmwood Park, NJ (800) 627-1479
Guardant HealthGuardant Health
Redwood City, CA
Redwood City, CA (855) 698-8887
Integrated Oncology / LabCorp
Integrated Oncology /

Phoenix, AZ
Phoenix, AZ AZ: (800) 710-1800
CT/NY: (800) 447-5816
TN: (800) 874-8532
Mayo Clinic LaboratoriesMayo Clinic Laboratories
Rochester, MN
Rochester, MN (800) 533-1710
or (507) 266-5700
NeoGenomics LaboratoriesNeoGenomics Laboratories
Fort Myers, FL
Fort Myers, FL (866) 776-5907
(option 3)
Sacramento, CA
Sacramento, CA (916) 252-0068
Paradigm Cancer DiagnosticsParadigm Cancer Diagnostics
Phoenix, AZ
Phoenix, AZ (844) 232-4719
Hayward, CA
Hayward, CA (650) 300-2188
Quest DiagnosticsQuest Diagnostics
Teterboro, NJ
Teterboro, NJ (866) 697-8378
Strata OncologyStrata Oncology
Ann Arbor, MI
Ann Arbor, MI (734) 527-1000
Chicago, IL
Chicago, IL (800) 739-4137
TriCore Reference LaboratoriesTriCore Reference Laboratories
Albuquerque, NM
Albuquerque, NM (505) 938-8888
or (800) 245-3296

The above is a list of facilities with high testing volume that are CLIA certified and accept external samples. CLIA certification was validated using the CDC website, and acceptance of external samples was confirmed by reviewing facility websites and/or contacting facilities directly. Amgen neither recommends nor endorses, and may or may not have financial relationships with, any facility that appears on this list. This list is not intended to be a comprehensive list nor as a referral to any lab listed. If you would like to suggest a facility to be added to this list, please contact Amgen MedInfo at 800-77-AMGEN.

This information is current as of September 9, 2021. Amgen does not guarantee the accuracy of this information, and it is up to the individual healthcare professional to conduct his/her own research.


Considerations that your multidisciplinary team (MDT) may find helpful when reporting biomarker results

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    Your MDT may include oncologists, pathologists, pulmonologists, nurse practitioners, physician assistants, nurse navigators, office staff, and others37,38

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    Consider using the upfront summary of your reporting template to document actionable biomarkers7

    • Pathologist associations offer templates that can guide reporting of actionable biomarkers, like KRAS G12C

    Consider uniform and unambiguous nomenclature (ie, KRAS G12C)7

    • Some reports (eg, analytical) may present KRAS G12C results as 12Cys, Gly12Cys (GGT or TGT), or p.G12C39
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    Consider recording patients’ biomarker status in your notes or their chart for ease of future reference40

    • For KRAS G12C, specifically note G12C to differentiate from other KRAS mutations
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    Consider using a set location for reports for easy access by all members of the MDT40

    • A discussion among the MDT may help establish the optimal location and a clear, easily identifiable file naming system
    • Some reports may be retrieved via fax, email, lab portals, or directly from the EMR

ALK, anaplastic lymphoma kinase; AMP, Association for Molecular Pathology; ASCO, American Society of Clinical Oncology; BRAF, proto-oncogene B-Raf; CAP, College of American Pathologists; CDC, Centers for Disease Control and Prevention; cfDNA, circulating free DNA; CLIA, Clinical Laboratory Improvement Amendments; CTC, circulating tumor cells; ctDNA, circulating tumor DNA; EGFR, epidermal growth factor receptor; EMR, electronic medical record; ERBB2, erb-B2 receptor tyrosine kinase 2; FFPE, formalin-fixed, paraffin-embedded; GGT, glycine; HER2, human epidermal growth factor receptor 2; IASLC, International Association for the Study of Lung Cancer; IHC, immunohistochemistry; KRAS, Kirsten rat sarcoma; MET, mesenchymal epithelial transition; mNSCLC, metastatic non-small cell lung cancer; n/a, not applicable; NCCN, National Comprehensive Cancer Network; NGS, next-generation sequencing; NPV, negative predictive value; NSCLC, non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; PCR, polymerase chain reaction; PD-L1, programmed cell death ligand 1; PPV, positive predictive value; RET, rearranged during transfection; ROS1, c-ros oncogene 1; TGT, cysteine.