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    BIOMARKER:

    EGFR C797S + 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:
    1956; 4233
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    13d
    The potential role of next-generation sequencing in identifying MET amplification and disclosing resistance mechanisms in NSCLC patients with osimertinib resistance. (PubMed, Front Oncol)
    The known resistance mechanisms, including MET amplification, EGFR (C797S, L718Q/R), TP53, CDK4, CDK6, CDKN2A, BRAF, KRAS, NRAS and PIK3CA mutations were also disclosed in our cohort. NGS assay can achieve a high concordance with FISH in MET amplification detection and has advantages in portraying various genetic alterations, which is of worthy in clinical promotion.
    Journal • Next-generation sequencing
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NRG1 (Neuregulin 1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
    |
    TP53 mutation • EGFR mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • MET amplification • EGFR T790M • EGFR C797S • EGFR L718Q • BRAF amplification • EGFR C797S + MET amplification
    |
    Tagrisso (osimertinib)
    1year
    Acquired mechanisms of resistance to first-line (1L) osimertinib with or without platinum-based chemotherapy (CT) in EGFR-mutated (EGFRm) advanced NSCLC: Preliminary data from FLAURA2 (ESMO Asia 2023)
    Methods Pts with treatment-naïve, EGFRm advanced NSCLC received osi + CT (osi 80 mg once daily [QD] + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 or carboplatin AUC5 every 3 weeks [Q3W] for 4 cycles, followed by osi 80 mg QD + pemetrexed 500 mg/m2 Q3W) or osi monotherapy (80 mg QD) until PD/discontinuation criterion. Osi + CT resulted in similar resistance mechanisms to osi monotherapy, and should not impact subsequent targeted second-line tx options. This analysis was enriched with pts who had early progression; further follow-up is required.
    Clinical • Metastases
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    EGFR mutation • MET amplification • EGFR C797S • EGFR C797S + MET amplification
    |
    GuardantOMNI
    |
    cisplatin • Tagrisso (osimertinib) • carboplatin • pemetrexed
    over1year
    Analysis of ctDNA next generation sequencing (NGS) for predicting response to amivantamab and lazertinib among patients with EGFR-mutant NSCLC after progression on osimertinib and platinum-based chemotherapy (CHRYSALIS-2 Cohort A) (AACR 2023)
    Among pts who progressed on osi and platinum-based chemotherapy, genetic profiling of osi resistance by ctDNA did not predict response, with many responders having unknown resistance mechanisms. These results suggest alternative biomarker approaches are needed to identify pts most likely to benefit from ami + laz.Table. ORR by type of resistance mechanismResistance mechanismnPRORRaEGFR/MET-dependentb28829%EGFR/MET-independent31826%Unknown512039%All patients1103633%aResponses were assessed by blinded independent central review per RECIST v1.1.
    Clinical • Next-generation sequencing • Circulating tumor DNA
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    TP53 mutation • EGFR mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR C797S • EGFR C797S + MET amplification
    |
    Guardant360® CDx
    |
    Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)