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Amplificación de MET de alto nivel (relación MET/CEP7 ≥4,0 O media GCN ≥10) en NSCLC metastásico —...

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IDRF-NSCLC-MET-AMP-ACTIONABLE
TipoSeñal de alerta
Situaciónreviewed 2026-04-29 | pending_clinical_signoff
EnfermedadesDIS-NSCLC
FuentesSRC-ESMO-NSCLC-METASTATIC-2024 SRC-GEOMETRY-WOLF-2020 SRC-NCCN-NSCLC-2025

Origen de la bandera roja

DefiniciónHigh-level MET amplification (MET/CEP7 ratio ≥4.0 OR mean GCN ≥10) in metastatic NSCLC — distinct from MET ex14 skipping. Two contexts: (1) De-novo MET-amp NSCLC (~1-5%) — capmatinib (GEOMETRY mono-1 high-amp cohort: ORR 40%, mPFS 5.5 mo; off-label expansion beyond ex14 label). (2) Acquired MET-amp post-osimertinib resistance in EGFR-mut NSCLC — osimertinib + savolitinib (SAVANNAH; not yet FDA- approved). Low-level amp (GCN 5-9) NOT actionable.
Dirección clínicaintensificar
Categoríahigh-risk-biology
Algoritmo de cambiosALGO-NSCLC-METASTATIC-2L

Lógica de activación

{
  "any_of": [
    {
      "finding": "met_amplification",
      "value": true
    },
    {
      "finding": "met_amplification",
      "value": "positive"
    },
    {
      "finding": "met_amp",
      "value": "positive"
    },
    {
      "finding": "met_cep7_ratio_ge_4",
      "value": true
    },
    {
      "finding": "met_gcn_ge_10",
      "value": true
    },
    {
      "finding": "met_status",
      "value": "amplified"
    }
  ],
  "type": "biomarker"
}

Notas

GEOMETRY mono-1 enrolled MET-amp cohort by GCN strata: GCN ≥10 cohort (high-amp) showed clinically meaningful response to capmatinib; GCN 6-9 cohort showed minimal benefit. Detection: FISH (Cappuzzo / Schildhaus criteria — MET/CEP7 ≥4 = high-level) preferred; NGS copy-number calls require assay-specific high-amp threshold. IHC alone is screening only — confirmation by FISH or NGS required. EGFR-mut NSCLC progressing on osimertinib: MET-amp is dominant non-T790M resistance mechanism; SAVANNAH (osi + savolitinib) showed ORR ~49% but not FDA-approved (covered indirectly by amivantamab + lazertinib via MET arm in MARIPOSA-2). Routes via ALGO-NSCLC-METASTATIC-2L step-10 area (parallel to MET ex14 — capmatinib regimen reused).

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Algoritmos