While the KRAS G12C mutation is most commonly found in smokers, it can occur regardless of clinical or demographic characteristics8
While the KRAS G12C mutation is most commonly found in smokers, it can occur regardless of clinical or demographic characteristics8
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
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing for KRAS G12C in all patients with advanced* NSCLC2,†,‡
CAP/IASLC/AMP and ASCO Guidelines recommend testing for actionable biomarkers (eg, KRAS G12C) utilizing either a comprehensive panel or targeted testing4
Support the ability of all NSCLC patients to obtain and understand their biomarker test results
*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
*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
A broad panel uses less tissue than a series of single-gene tests, so additional tests can be run if needed9
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
Expanded-panel testing at diagnosis may take less time than consecutive single-gene tests in a process-of-elimination approach13
Expanded panel testing provides results for many biomarkers in one report rather than multiple different reports14
Most NGS platforms already test for KRAS G12C. There are also many PCR platforms capable of KRAS G12C testing5
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 |
| Limitations |
|
*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
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
NSCLC liquid biopsy options exist29,30
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,‡
*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
*FDA-approved targeted therapies included EGFR, ALK, ROS1, and BRAF.15
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
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.
Your MDT may include oncologists, pathologists, pulmonologists, nurse practitioners, physician assistants, nurse navigators, office staff, and others37,38
Consider using the upfront summary of your reporting template to document actionable biomarkers7
Consider uniform and unambiguous nomenclature (ie, KRAS G12C)7
Consider recording patients’ biomarker status in your notes or their chart for ease of future reference40
Consider using a set location for reports for easy access by all members of the MDT40
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.
