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    BIOMARKER:

    HER-2 amplification + MET amplification

    i
    Other names: ERBB2, CD340, HER-2, HER2, NEU, NGL, V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2, 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:
    2064; 4233
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    3ms
    Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer. (PubMed, Nat Med)
    The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .
    Journal • Circulating tumor DNA • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
    |
    HER-2 amplification • NTRK1 fusion • MET amplification • PTEN mutation • RAS wild-type • MET mutation • HER-2 amplification + MET amplification
    |
    Avastin (bevacizumab) • Vectibix (panitumumab) • oxaliplatin
    4ms
    Comparison of an amplicon-based large panel next generation sequencing (NGS) assay with conventional testing methods for MET and HER2 amplification in lung and breast cancers. (PubMed, Pathology)
    The low sensitivity for HER2 amplification may be confounded by the small sample size and disproportionate number of cases with low level amplification. In summary, the NGS assay has good concordance with conventional testing methods but may be less sensitive in detecting low level gene amplification.
    Journal • Next-generation sequencing
    |
    HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    HER-2 positive • HER-2 amplification • HER-2 negative • MET amplification • HER-2 amplification + MET amplification
    over1year
    Negative hyperselection of patients with RAS wild-type metastatic colorectal cancer for panitumumab: A biomarker study of the phase III PARADIGM trial. (ASCO-GI 2023)
    Background: The PARADIGM trial showed longer median overall survival (OS) with first-line mFOLFOX6 plus panitumumab (PAN) vs bevacizumab (BEV) in patients (pts) with RAS wild type (WT) and left-sided metastatic colorectal cancer (mCRC) (37.9 vs 34.3 months, respectively; hazard ratio [HR], 0.82; P=0.031) and similar OS in right-sided pts (HR 1.09; Yoshino T, et al... Negative hyperselection using ctDNA rather than tumor sidedness may identify appropriate pts for first-line PAN over BEV. These results warrant further validation in additional cohorts. Clinical trial information: NCT02394834.
    Clinical • P3 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • RAS (Rat Sarcoma Virus)
    |
    BRAF V600E • HER-2 amplification • BRAF V600 • NTRK1 fusion • MET amplification • PTEN mutation • RAS wild-type • MET mutation • HER-2 amplification + MET amplification
    |
    Avastin (bevacizumab) • 5-fluorouracil • Vectibix (panitumumab) • oxaliplatin • leucovorin calcium
    over1year
    Negative hyperselection of patients with RAS wild-type metastatic colorectal cancer for panitumumab: A biomarker study of the phase III PARADIGM trial. (ASCO-GI 2023)
    Background: The PARADIGM trial showed longer median overall survival (OS) with first-line mFOLFOX6 plus panitumumab (PAN) vs bevacizumab (BEV) in patients (pts) with RAS wild type (WT) and left-sided metastatic colorectal cancer (mCRC) (37.9 vs 34.3 months, respectively; hazard ratio [HR], 0.82; P=0.031) and similar OS in right-sided pts (HR 1.09; Yoshino T, et al... Negative hyperselection using ctDNA rather than tumor sidedness may identify appropriate pts for first-line PAN over BEV. These results warrant further validation in additional cohorts. Clinical trial information: NCT02394834.
    Clinical • P3 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • RAS (Rat Sarcoma Virus)
    |
    BRAF V600E • HER-2 amplification • BRAF V600 • NTRK1 fusion • MET amplification • PTEN mutation • RAS wild-type • MET mutation • HER-2 amplification + MET amplification
    |
    Avastin (bevacizumab) • 5-fluorouracil • Vectibix (panitumumab) • oxaliplatin • leucovorin calcium
    2years
    Next Generation Sequencing of Circulating Tumor DNA Can Optimize Second Line Treatment in RAS Wild Type Metastatic Colorectal Cancer after Progression on Anti-EGFR Therapy: Time to Rethink Our Approach. (PubMed, Oncol Res Treat)
    NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.
    Clinical • Review • Journal • Next-generation sequencing • Circulating tumor DNA
    |
    MET (MET proto-oncogene, receptor tyrosine kinase) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF mutation • HER-2 amplification • MET amplification • RAS wild-type • HER-2 amplification + MET amplification
    2years
    Multiplex Droplet Digital PCR Assay for Detection of MET and HER2 Genes Amplification in Non-Small Cell Lung Cancer. (PubMed, Cancers (Basel))
    Among the tested samples, five specimens (1.15%) showed a higher ratio of MET, and six samples (1.38%) showed a higher ratio of HER2. The reported multiplex ddPCR assay could be used for the routine screening of MET and HER2 amplification in NSCLC samples.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    HER-2 amplification • MET amplification • EGFR negative • HER-2 amplification + MET amplification
    over2years
    Real-World Approach for Molecular Analysis of Acquired EGFR Tyrosine Kinase Inhibitor Resistance Mechanisms in NSCLC. (PubMed, JTO Clin Res Rep)
    With the approval of first-line osimertinib treatment in stage IV EGFR-mutated NSCLC, detection of resistance mechanisms will become increasingly important-and complex...In case of financial or tissue limitations, a sequential approach is justifiable, in which RNA NGS is only performed in case no resistance mechanisms are identified. Yet, this is suboptimal as-although rare-multiple acquired resistance mechanisms may occur.
    Clinical • Journal • Real-world evidence
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    EGFR mutation • HER-2 amplification • MET amplification • HER-2 amplification + MET amplification
    |
    Tagrisso (osimertinib)