MET exon 14 skipping — ~3-4% of NSCLC adenocarcinoma; older / smoker enriched. Capmatinib...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-NSCLC-MET-EX14-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-GEOMETRY-WOLF-2020` `SRC-NCCN-NSCLC-2025` `SRC-VISION-PAIK-2020`

Red Flag Origin

Definition	MET exon 14 skipping — ~3-4% of NSCLC adenocarcinoma; older / smoker enriched. Capmatinib (GEOMETRY mono-1 — ORR 41-68%) and tepotinib (VISION) are FDA-approved selective MET-TKIs for any-line use. RNA-NGS preferred for splice-site detection.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-1L, ALGO-NSCLC-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "met_ex14_skipping",
      "value": true
    },
    {
      "finding": "met_exon14_skipping",
      "value": "positive"
    },
    {
      "finding": "met_alteration",
      "value": "Ex14 skipping"
    },
    {
      "finding": "met_status",
      "value": "ex14_skipping"
    }
  ],
  "type": "biomarker"
}

Notes

GEOMETRY mono-1 / VISION enrolled both 1L and 2L+ — TKI is a reasonable 1L option, though some MTBs still default to chemo + IO in 1L and reserve MET-TKI for 2L. Toxicity: peripheral edema (60-80%), hypoalbuminemia, creatinine elevation (TKI competition with creatinine secretion — pseudo-elevation, not true AKI). MET amplification (high-level GCN ≥10) is a separate actionable subset — covered by BIO-MET amplification status.

Used By

Algorithms

ALGO-NSCLC-METASTATIC-1L - ALGO-NSCLC-METASTATIC-1L
ALGO-NSCLC-METASTATIC-2L - ALGO-NSCLC-METASTATIC-2L