METex14 ALTERATIONS ARE ASSOCIATED WITH POOR PROGNOSIS IN NSCLC1

 

 

METex14 is an oncogenic alteration in non-small cell lung cancer2

 

METex14 diagram

 

  • METex14 alterations can result in overstimulation of the MET pathway3,4
    • METex14 alterations lead to deletion of the juxtamembrane domain, which is involved in MET protein degradation, resulting in the persistence and overabundance of MET receptors
  • METex14 alterations can occur early and are present throughout NSCLC development1,2
  • Many patients are not diagnosed with NSCLC until their disease has progressed to later stages2

 

Patients with METex14 non-small cell lung cancer face a poor prognosis1,5

   

 

METex14 was found to be an independent prognostic factor that predicted worse survival compared with patients without MET alteration.1,5,6

 

 

METex14 NSCLC may occur in up to 5,800 patients in the United States and 53,300 patients worldwide per year7-9

 

 

  • In NSCLC, brain, bone, and liver metastases may be indicative of worsening outcomes10

 

NSCLC patients
Based on a retrospective analysis (N=543)10a
NSCLC patients

Based on a retrospective analysis (N=543)10a

~22%
~39%
~11%
 
Brain metastasis
Bone metastasis
Liver metastasis
METex14 NSCLC patients
Based on a retrospective analysis (N=148)11,12b
METex14 NSCLC patients
Based on a retrospective analysis (N=148)11,12b
37%
49%
20%

aData from a retrospective study evaluating 543 patients with stage IV NSCLC, including 121 patients who tested positive for EGFR mutations. Patients were evaluated for the impact of EGFR mutations on the pattern of metastasis.
bData from a retrospective study evaluating 148 patients with stage IV METex14 NSCLC. Sites of metastases were studied as part of the clinicopathologic characteristics of the patient.

 

METex14 alterations result in sustained oncogenic MET signaling, contributing to poor prognosis and highlighting the importance of knowing if your patients have METex14 NSCLC13

 

HGF, hepatocyte growth factor; NSCLC, non-small cell lung cancer.

 

 

References

1. Tong JH, Yeung SF, Chan AWH, et al. Clin Cancer Res. 2016;22(12):3048-3056.
2. Drilon A, Cappuzzo F, Ou SI, Camidge DR. J Thorac Oncol. 2016;12(1):15-26.
3. Reungwetwattana T, Ou SH. Transl Lung Cancer. 2015;4(6):820-824.
4. Ma PC. Cancer Discov. 2015;5(8):802-805.
5. Yeung SF, Tong JHM, Law PPW, et al. J Thorac Oncol. 2015;10(9):1292-1300.
6. Katalinic D, Aleric I, Vcev A. MET exon 14 splicing mutation and its correlation with clinicopathological features in subjects with non-small cell lung cancer. Poster presented at: ESMO 2018 Congress; October 20, 2018; Munich, Germany.
7. Awad MM, Oxnard GR, Jackman DM, et al. J Clin Oncol. 2016;34(7):721-730.
8. National Cancer Institute, SEER Program. Cancer stat facts: lung and bronchus cancer. 2016. https://seer.cancer.gov/statfacts/html/lungb.html. Accessed October 11, 2019.
9. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. CA Cancer J Clin. 2018;68(6):394-424.
10. Hsu F, De Caluwe A, Anderson D, Nichol A, Toriumi T, Ho C. Curr Oncol. 2017;24(4):228-233.
11. Awad MM, Leonardi GC, Kravets S, et al. Lung Cancer. 2019;133:96-102.
12. Awad MM, Leonardi GC, Kravets S, et al. Lung Cancer (suppl). 2019;133:96-102.
13. Ariyawutyakorn W, Saichaemchan S, Varella-Garcia M. J Cancer. 2016;7(6):633-649.

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