Advanced NSCLC Biomarker Testing for KRAS G12C
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Lead the way—find KRAS G12C, the most prevalent emerging biomarker in NSCLC1,2

Consider testing for KRAS G12C to find the unseen 13%1:

who-to-test

Who to Test

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Consider testing eligible patients with advanced NSCLC for KRAS at diagnosis2,3

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why-to-test

Why to Test

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  • Highly prevalent1
  • KRAS is recognized by national clinical guidelines4,5
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how-to-test-and-report

How to Test and Report

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  • Included in most NGS panels and can be tested by PCR7-9
  • Use FFPE tissue or liquid biopsy specimens10
  • Report specifically at the G12C variant level11
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Who to Test

Consider testing for KRAS in eligible patients with NSCLC at diagnosis4,5

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    While KRAS mutations are most commonly found in smokers, they can occur regardless of clinical or demographic characteristics12

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    Guidelines recommend testing for both actionable and emerging biomarkers (including KRAS) in patients with advanced NSCLC2,4,5

Why to Test

The NSCLC landscape is evolving—
Check your biomarker panel for emerging biomarkers like KRAS2

KRAS mutations often occur early and persist as the disease progresses13,14

  • 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 testing5

*Includes patients with advanced/metastatic NSCLC, but not locally advanced NSCLC.6

†It is recommended at this time that when feasible, molecular testing be performed via a broad, panel-based approach, most typically performed by NGS.6

‡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.6

Guidelines recognize the value of knowing KRAS status in advanced NSCLC

table-3-2table-3-2 

*It is recommended at this time that when feasible, molecular testing be performed via a broad, panel-based approach, most typically performed by NGS.6
†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.6
‡Includes patients with advanced/metastatic NSCLC, but not locally advanced NSCLC.6
§Note: In June 2020, the FDA approved immunotherapy for unresectable or metastatic TMB-high solid tumors.15

Consider comprehensive genomic profiling at diagnosis to identify actionable and emerging biomarkers

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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 needed2

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    Cost-effective

    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 rebiopsy2,16

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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 approach16

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    Consistent reporting

    Expanded panel testing provides results for many biomarkers in one report rather than multiple different reports17

KRAS G12C is already included in most NGS panels and can also be detected by currently available PCR and Sanger sequencing methods.7-9,18

How to Test and Report

The KRAS G12C point mutation can be detected in tissue and liquid biopsy specimens using common molecular testing methods7,18,19

KRAS G12C results may already be in your report

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    Most NGS platforms already test for KRAS G12C. There are also many PCR platforms capable of KRAS G12C testing7-9,18

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    Tissue in NSCLC remains the gold standard—and liquid biopsy shows a high degree of concordance10,19

  NGS (FFPE sample) PCR (FFPE sample)
Reliability* 1%–10% sensitivity, 95%-100% specificity2,7,20 1%–5% sensitivity, 96%–100% specificity18,20-22
DNA/RNA Input 10–1000 ng DNA/10–200 ng RNA7,20,23,24 5–300 ng DNA/50–1000 ng RNA20,21,25-27
Turnaround Time2,20,22 4–14 days† 1–7 days
Limitations
  • Specialty infrastructure required28
  • Variable sensitivity and specificity across assays2
  • 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 testing5
    • Consider listing KRAS G12C at the variant level in your reports, as some analytical reports may not specify this mutation11

*Includes whole genome and targeted NGS analyses and quantitative/real-time and digital PCR analyses.
†CAP/IASLC/AMP Guidelines recommend a turnaround time of no more than 10 days.5

Liquid biopsy may be an alternative to tissue-based testing29

biopsy-desk  biopsy-mob 

Image reproduced with permission from Pantel et al.30

One form of liquid biopsy consists of obtaining ctDNA from plasma, which can be used to identify genomic alterations5,30

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

Liquid biopsy may be used with high degrees of concordance19

  • Up to 25% of patients are ineligible for rebiopsy. If tissue biopsy isn’t an option for your patient, liquid biopsy may be an alternative31
cfDNA vs tissue-based testing for KRAS mutations in patients with mNSCLC19*
cfDNA_vs_Tissue_Chart  cfDNA_vs_Tissue_Chart 

Liquid biopsy allows for detection of biomarkers when tissue is not available19

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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 guidelines19‡

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 alone3,29

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    FDA-approved liquid biopsy tests are already available for some NSCLC biomarkers32

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    Both the CAP/IASLC/AMP guidelines and an IASLC consensus paper support the utility of a positive liquid biopsy result5,29

*Concordance and PPV for the other guideline-recommended biomarkers was similarly high.19
†The number of patients identified to have driver mutation increased from 60 to 89, including those with negative, not assessed, or insufficient tissue results.19
‡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).19

Comparing tissue and liquid biopsy testing

*FDA-approved targets included EGFR, ALK, ROS1, and BRAF.

Where to Test

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    FOR ONCOLOGISTS

    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 https://www.aruplab.com (800) 522-2787
https://www.aruplab.com
BioceptBiocept
San Diego, CA		 San Diego, CA https://biocept.com (888) 332-7729
https://biocept.com
BiodesixBiodesix
Boulder, CO		 Boulder, CO https://www.biodesix.com (866) 432-5930
https://www.biodesix.com
Caris Life SciencesCaris Life Sciences
Phoenix, AZ		 Phoenix, AZ https://www.carislifesciences.com (888) 979-8669
https://www.carislifesciences.com
Circulogene TheranosticsCirculogene Theranostics
Birmingham, AL		 Birmingham, AL https://circulogene.com (855) 614-7083
https://circulogene.com
Foundation MedicineFoundation Medicine
Cambridge, MA		 Cambridge, MA https://www.foundationmedicine.com (888) 988-3639
https://www.foundationmedicine.com
GenPath DiagnosticsGenPath Diagnostics
Elmwood Park, NJ		 Elmwood Park, NJ https://www.genpathdiagnostics.com (800) 627-1479
https://www.genpathdiagnostics.com
Guardant HealthGuardant Health
Redwood City, CA		 Redwood City, CA https://guardanthealth.com (855) 698-8887
https://guardanthealth.com
LabCorp /
Integrated Oncology /
US LabsLabCorp /
Integrated Oncology /
US Labs
Phoenix, AZ		 Phoenix, AZ https://www.labcorp.com AZ: (800) 710-1800
CT/NY: (800) 447-5816
TN: (800) 874-8532
https://www.labcorp.com
Mayo Clinic LaboratoriesMayo Clinic Laboratories
Rochester, MN		 Rochester, MN https://www.mayocliniclabs.com (800) 533-1710
or (507) 266-5700
https://www.mayocliniclabs.com
NeoGenomics LaboratoriesNeoGenomics Laboratories
Aliso Viejo, CA		 Aliso Viejo, CA https://neogenomics.com/ (866) 776-5907
(option 3)
https://neogenomics.com/
Novogene Corporation Inc.Novogene Corporation Inc.
Sacramento, CA		 Sacramento, CA https://en.novogene.com (916) 252-0068
https://en.novogene.com
Paradigm Cancer DiagnosticsParadigm Cancer Diagnostics
Phoenix, AZ		 Phoenix, AZ https://www.paradigmdx.com (844) 232-4719
https://www.paradigmdx.com
PredicinePredicine
Hayward, CA		 Hayward, CA https://www.predicine.com (650) 300-2188
https://www.predicine.com
Quest DiagnosticsQuest Diagnostics
Teterboro, NJ		 Teterboro, NJ https://www.questdiagnostics.com (866) 697-8378
https://www.questdiagnostics.com
TempusTempus
Chicago, IL		 Chicago, IL https://www.tempus.com (800) 739-4137
https://www.tempus.com
TriCore Reference LaboratoriesTriCore Reference Laboratories
Albuquerque, NM		 Albuquerque, NM http://www.tricore.org/home (505) 938-8888
or (800) 245-3296
http://www.tricore.org/home

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 8, 2020. Amgen does not guarantee the accuracy of this information, and it is up to the individual healthcare professional to conduct his/her own research.

Reporting

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 others39,40

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    FOR PATHOLOGISTS

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    FOR PATHOLOGISTS

    Consider using the upfront summary of your reporting template to document both actionable and emerging biomarkers11

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

    Consider uniform and unambiguous nomenclature (ie, KRAS G12C)11

    • Some reports (eg, analytical) may present KRAS G12C results as 12Cys or Gly12Cys (GGT or TGT)
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    FOR ONCOLOGISTS

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    FOR ONCOLOGISTS

    Consider recording patients’ biomarker status in your notes or their chart for ease of future reference33

    • For KRAS G12C, specifically note G12C to differentiate from other KRAS mutations
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    FOR ALL MULTIDISCIPLINARY TEAM MEMBERS

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    FOR ALL MULTIDISCIPLINARY TEAM MEMBERS

    Consider using a set location for reports for easy access by all members of the MDT11,33

    • 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
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Download the KRAS G12C Biomarker Fact Sheet
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Download the KRAS G12C—An Emerging Biomarker in NSCLC Slide Deck

ALK, anaplastic lymphoma kinase; AMP, Association for Molecular Pathology; ASCO, American Society of Clinical Oncology; BRAF, v-Raf murine sarcoma viral oncogene homolog B; CAP, College of American Pathologists; 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, v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2; FFPE, formalin-fixed, paraffin-embedded; GGT, glycine; HER2, human epidermal growth factor receptor 2; IASLC, International Association for the Study of Lung Cancer; KRAS, Kirsten rat sarcoma; MET, mesenchymal epithelial transition; METex14, MET exon 14; mNSCLC, metastatic NSCLC; NCCN, National Comprehensive Cancer Network; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; NTRK, neurotrophic-tropomyosin receptor kinase; PCR, polymerase chain reaction; PD-L1, programmed cell death ligand 1; PPV, positive predictive value; RET, rearranged during transfection; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase; TGT, cysteine; TMB, tumor mutational burden.