MET Amplification and Response to MET Inhibitors in Stage IV Lung Adenocarcinoma.
BACKGROUND
Non-small-cell lung cancers with MET amplification may respond to c-MET inhibitors.


METHODS
We examined lung adenocarcinoma patients for mutations and amplification status of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS, MET. The clinical characteristics of patients with MET amplification and their responses to MET inhibitor therapy were studied.


RESULTS
Of the 76 patients analyzed, 5 were positive for c-MET gene amplification and 4 cases showed an intermediate result. For 12 patients who were EGFR positive, a c-MET analysis on secondary biopsy tissue was performed following disease progression. All 5 c-MET-positive patients were men. The age range in the study was 34-83 years. 4 of the 5 patients were started on crizotinib. 2 of these cases were positive following tyrosine kinase inhibitor therapy. 3 patients showed a response. 1 patient showed no response and was later found to have a concurrent T790M mutation.


CONCLUSIONS
There are 2 categories of MET gene amplification in lung cancer patients, de novo and that secondary to TKI therapy. These patients can benefit from MET inhibitor therapy. Dual mechanisms of resistance, EGFR T790M mutation and c-MET amplification after TKI therapy, may suggest a poor prognosis.
Moushumi
M
Suryavanshi
Aekta
A
Shah
Dushyant
D
Kumar
Manoj K
MK
Panigrahi
Anurag
A
Metha
Ullas
U
Batra
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met