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BIOMARKER:

EGFR mutation + MET amplification

i
Other names: EGFR, ERBB, ERBB1, Epidermal growth factor receptor, DFNB97, AUTS9, RCCP2, C-Met, HGFR, HGF Receptor, Met Proto-Oncogene, HGF/SF Receptor, Proto-Oncogene C-Met, Scatter Factor Receptor, Tyrosine-Protein Kinase Met, Hepatocyte Growth Factor Receptor, MET, MET Proto-Oncogene, Receptor Tyrosine Kinase
Entrez ID:
11ms
Randomized Trial of Tepotinib Plus Gefitinib Versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis. (PubMed, Clin Cancer Res)
Final analysis of INSIGHT suggests improved PFS and OS with tepotinib plus gefitinib versus chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC, after progression on EGFR inhibitors.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • MET amplification • MET mutation • EGFR mutation + MET amplification • EGFR mutation + MET-CEP7 fusion
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gefitinib • Tepmetko (tepotinib)
11ms
Phase 1b study of HS-10241 combined with almonertinib in pre-treated advanced non-small cell lung cancer (NSCLC) harboring EGFR mutation. (ASCO 2023)
HS-10241 in combination with almonertinib was well tolerated, and showed encouraging antitumor activity in treatment of advanced NSCLC with EGFR mutation and MET amplification following prior EGFR-TKI, whether MET GCN ≥10 or MET GCN ≥5 but < 10. Clinical trial information: NCT05430386.
P1 data • Metastases
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • MET amplification • MET mutation • MET amplification + EGFR mutation • EGFR mutation + MET amplification • EGFR mutation + MET-CEP7 fusion
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Ameile (aumolertinib) • HS-10241
over1year
Savolitinib monotherapy exerted significant benefit in a non-small cell lung cancer patient with osimertinib resistance harboring primary EGFR L858R mutation and MET amplification: a case report. (PubMed, Anticancer Drugs)
Here, we described a case of a 64-year-old male with lung adenocarcinoma presented primary resistance on osimertinib combined with bevacizumab and platinum-based chemotherapy, next-generation sequencing revealed EGFR exon 21 L858R mutation and MET gene amplification. Our case highlights that EGFR-TKIs may be not the optimal choice for lung adenocarcinoma with primary EGFR-sensitive mutation with MET amplification simultaneously, whereas MET inhibitor alone may be an effective treatment option. In clinical practice, we should fully consider the possibility of primary resistance in EGFR-TKIs administration.
Journal
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • EGFR L858R • MET amplification • MET mutation • EGFR positive • EGFR mutation + MET amplification • EGFR L858R + MET amplification
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Avastin (bevacizumab) • Tagrisso (osimertinib) • Orpathys (savolitinib)
over2years
MET inhibition downregulates DR4 expression in MET-amplified lung cancer cells with acquired resistance to EGFR inhibitors through suppressing AP-1-mediated transcription. (PubMed, Neoplasia)
Osimertinib combined with MET inhibition synergistically induces apoptosis in the MET-amplified EGFR mutant NSCLC cells accompanied with augmented DR4 reduction both in vitro and in vivo. Furthermore, MET inhibition combined with TRAIL enhanced killing of MET-amplified EGFR mutant HCC827/AR cells, but not HCC827 parental cells. These data collectively suggest that DR4 may possess an unrecognized anti-apoptotic function, contributing to apoptosis resistance under given conditions.
Preclinical • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • MET amplification • EGFR expression • MET expression • AR mutation • EGFR mutation + MET amplification
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Tagrisso (osimertinib)