Actionable molecular driver detected (EGFR / ALK / ROS1 / KRAS G12C / BRAF V600E / MET ex...

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

ID	`RF-NSCLC-HIGH-RISK-BIOLOGY`
Type	Red flag
Status	pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-NCCN-NSCLC-2025`

Red Flag Origin

Definition	Actionable molecular driver detected (EGFR / ALK / ROS1 / KRAS G12C / BRAF V600E / MET ex14 / RET / NTRK / HER2 mut) — driver-targeted TKI / ADC takes precedence over ICI ± chemo regardless of PD-L1 TPS.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-1L

Trigger Logic

{
  "any_of": [
    {
      "finding": "BIO-EGFR-MUTATION",
      "value": "positive"
    },
    {
      "finding": "BIO-ALK-FUSION",
      "value": "positive"
    },
    {
      "finding": "BIO-ROS1-FUSION",
      "value": "positive"
    },
    {
      "finding": "BIO-KRAS-G12C",
      "value": "positive"
    },
    {
      "finding": "BIO-BRAF-V600E",
      "value": "positive"
    },
    {
      "finding": "met_ex14_skipping",
      "value": true
    },
    {
      "finding": "ret_fusion",
      "value": true
    },
    {
      "finding": "ntrk_fusion",
      "value": true
    },
    {
      "finding": "her2_mutation_nsclc",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

Driver-mutant NSCLC patients DO NOT benefit from ICI 1L (poorer responses, hyperprogression risk) — TKIs/ADCs are markedly superior. Universal NGS at diagnosis prevents missed-driver scenarios.

Used By

Algorithms

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