Acquired EGFR T790M (gatekeeper) mutation at progression on 1st/2nd-gen EGFR-TKI (gefitin...

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

ID	`RF-NSCLC-EGFR-T790M-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-FLAURA-SORIA-2018` `SRC-NCCN-NSCLC-2025`

Red Flag Origin

Definition	Acquired EGFR T790M (gatekeeper) mutation at progression on 1st/2nd-gen EGFR-TKI (gefitinib, erlotinib, afatinib, dacomitinib) — drives 2L switch to osimertinib (AURA3 — mPFS 10.1 vs 4.4 mo with platinum-pem). Detected on ctDNA NGS or tissue re-biopsy.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "egfr_t790m",
      "value": true
    },
    {
      "finding": "egfr_t790m",
      "value": "positive"
    },
    {
      "finding": "egfr_mutation",
      "value": "T790M"
    }
  ],
  "type": "biomarker"
}

Notes

T790M presence at first progression on older TKI = osimertinib 2L with established benefit. With osimertinib used 1L (FLAURA standard), T790M is a rare resistance mechanism — most progression on osimertinib shows alternate mechanisms (C797S, MET amp, transformation). ctDNA at progression is preferred (avoids re-biopsy morbidity); negative ctDNA → tissue re-biopsy because of false-negative rate.

Used By

Algorithms

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