It's time to DISCOVER MET in NSCLC

  • Did you know?
    The MET pathway is dysregulated in NSCLC1,2
    MET/c-Met protein overexpression, MET gene
    amplification, and METex14 skipping mutations
    contribute to disease pathogenesis and are associated
    with poor prognosis
    Learn more about MET Aberrations in NSCLC
  • Did you know?
    c-Met protein overexpression is the most
    prevalent MET aberration3,4
    c-Met protein overexpression is an emerging biomarker in
    NSCLC, with ~25% prevalence in EGFR wild-type
    non-squamous NSCLC compared to ~2–4% for METex14
    skipping mutations and ~2–5% for MET gene amplification
    Review key prevalence information
  • Did you know?
    c-Met protein overexpression is an emerging
    biomarker and requires IHC analysis5,6
    IHC is an established testing modality in NSCLC. NGS and FISH are
    molecular tests and cannot be used to detect protein expression
    Explore MET testing examples
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EGFR=epidermal growth factor receptor; ex14=exon 14; FDA=Food and Drug Administration; FISH=fluorescence in situ hybridization; IHC=immunohistochemistry; MET=mesenchymal-epithelial transition; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer.

MET Aberrations

MET signaling in NSCLC is dysregulated through mechanisms including, but not limited to, c-Met protein overexpression, MET gene amplification, METex14 skipping mutations and HGF overexpression. MET aberrations are associated with poor prognosis in NSCLC3–7

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Overview
c-Met Protein Overexpression
MET Gene Amplification
METex14 Skipping Mutations
MET Aberrations
MET Aberrations

*EGFR-WT NSQ NSCLC. †Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.

EGFR=epidermal growth factor receptor; ex14=exon 14; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; NSCLC=non-small cell lung cancer; NSQ=non-squamous; WT=wild type.

c-Met Protein Overexpression
Cause4,9
Changes in epigenetic, transcriptional, and post-transcriptional regulation
Prevalence3*
~25%
Role as a Biomarker3,8
Emerging biomarker
Associated Therapies3,8
Target under clinical development
Testing Guidelines10†
Not included in existing guidelines
c-Met Protein Overexpression

*EGFR-WT NSQ NSCLC. †Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell lung Cancer V.7.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

EGFR=epidermal growth factor receptor; ex14=exon 14; FDA=Food and Drug Administration; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; NSCLC=non-small cell lung cancer; NSQ=non-squamous; WT=wild type.

MET Gene Amplification
Cause4
Increase in the number of copies of the MET gene
Prevalence4
~2–5%
Role as a Biomarker10*
Emerging biomarker
Associated Therapies7
No FDA-approved therapies currently available
Testing Guidelines10*
High-level MET amplification† is an emerging biomarker to identify novel therapies for patients with metastatic NSCLC
MET Gene Amplification

*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell lung Cancer V.7.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. †The definition of high-level MET amplification is evolving and may differ according to the assay used for testing. For NGS based results, a copy number greater than 10 is consistent with high-level MET amplification.10

ex14=exon 14; FDA=Food and Drug Administration; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer.

METex14 Skipping Mutations
Cause4,9
Disruption in mRNA splicing, resulting in the loss of a key regulatory domain and impaired c-Met protein degradation
Prevalence4
~2–4%
Role as a Biomarker7
FDA-approved CDx in NSCLC
Associated Therapies7
Small molecule tyrosine kinase inhibitors
Testing Guidelines10*
Testing recommended in advanced or metastatic disease to identify patients for targeted agents
METex14 Skipping Mutations

*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell lung Cancer V.7.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

CDx=companion diagnostics; ex14=exon 14; FDA=Food and Drug Administration; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; NSCLC=non-small cell lung cancer.

Due to their role in carcinogenesis and cancer progression, MET aberrations are emerging as biomarkers in NSCLC1,4,8

Cause3,4,8,9

Role as a
Biomarker3,7,8,10*

Prevalence3,4

MET Aberrations in NSCLC
c-Met Protein Overexpression

Changes in epigenetic, transcriptional, and post-transcriptional regulation

Emerging biomarker

~25%†

Cause3,4,8,9
Changes in epigenetic, transcriptional, and post-transcriptional regulation
Role as a Biomarker3,7,8
Emerging biomarker
Prevalence3,4
~25%†
MET Gene Amplification
MET Gene Amplification

Increase in the number of copies of the MET gene

Emerging biomarker

~2—5%

Cause3,4,8,9
Increase in the number of copies of the MET gene
Role as a Biomarker3,7,8,10*
Emerging biomarker
Prevalence3,4
~2—5%
METex14 Skipping Mutations
METex14 Skipping Mutations

Disruption in mRNA splicing

FDA-approved CDx

~2—4%

Cause3,4,8,9
Disruption in mRNA splicing
Role as a Biomarker3,7,8
FDA-approved CDx
Prevalence3,4
~2—4%

*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell lung Cancer V.7.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. †EGFR-WT NSQ NSCLC.

CDx=companion diagnostics; EGFR=epidermal growth factor receptor; ex14=exon 14; FDA=Food and Drug Administration; MET=mesenchymal-epithelial transition; NSCLC=non-small cell lung cancer; NSQ=non-squamous; WT=wild type.

Learn more about the methods
used to test for MET aberrations
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References
  1. Guo B, Cen H, Tan X, Liu W, Ke Q. Prognostic value of MET gene copy number and protein expression in patients with surgically resected non-small cell lung cancer: a meta-analysis of published literatures. PLoS One. 2014;9(6):e99399. doi:10.1371/journal.pone.0099399
  2. Lee GD, Lee SE, Oh DY, et al. MET exon 14 skipping mutations in lung adenocarcinoma: Clinicopathologic implications and prognostic values. J Thorac Oncol. 2017;12(8):1233-1246. doi:10.1016/j.jtho.2017.04.031
  3. Motwani M, Panchabhai S, Bar J, et al. P60.12 Prevalence of c-Met overexpression (c-Met+) and impact of prior lines of treatment on c-Met protein expression in NSCLC. J Thorac Oncol. 2021;16(10):S1169-S1170. doi:10.1016/j. jtho.2021.08.633
  4. Liang H, Wang M. MET oncogene in non-small cell lung cancer: mechanism of MET dysregulation and agents targeting the HGF/c-Met axis. Onco Targets Ther. 2020;13:2491-2510. doi:10.2147/OTT.S231257
  5. Park S, Choi YL, Sung CO, et al. High MET copy number and MET overexpression: poor outcome in non-small cell lung cancer patients. Histol Histopathol. 2012;27(2):197-207. doi:10.14670/HH-27.197
  6. Sun W, Song L, Ai T, et al. Prognostic value of MET, cyclin D1 and MET gene copy number in non-small cell lung cancer. J Biomed Res. 2013;27(3):220-230. doi:10.7555/JBR.27.20130004
  7. List of cleared or approved companion diagnostic devices. US Food and Drug Administration. Updated May 1, 2024. Accessed June 4, 2024. https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools
  8. Ansell PJ, Bailjal S, Liede A, et al. Prevalence and characterization of c-Met-overexpressing non-small cell lung cancer (NSCLC) across clinical trial samples and real-world patient cohorts from the City of Hope National Medical Center. Paper presented at: CRUK Lung Cancer Conference; Nov 15–17, 2022; Manchester, UK.
  9. Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G. Targeting MET in cancer: Rationale and progress. Nat Rev Cancer. 2012;12(2):89-103. doi:10.1038/nrc3205
  10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell lung Cancer V.7.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
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c-Met protein overexpression and MET amplification are emerging biomarkers and in clinical research as potential therapeutic targets. There are no FDA-approved tests for c-Met protein overexpression or MET amplification. Prognosis statements and prevalence estimates are based on multiple sources; survival and prevalence data can vary among studies and datasets because of detection methodology used, patient sample sizes and/or demographics/characteristics. Some patients may have more than one MET aberration and may have overlap with other NSCLC biomarkers.