ALK rearrangement / fusion (typically EML4-ALK) — ~5% of NSCLC adenocarcinoma; never-smok...

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

ID	`RF-NSCLC-ALK-FUSION-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-CROWN-SOLOMON-2021` `SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-NCCN-NSCLC-2025`

Red Flag Origin

Definition	ALK rearrangement / fusion (typically EML4-ALK) — ~5% of NSCLC adenocarcinoma; never-smoker / younger enriched. Treatment-defining: alectinib (ALEX — mPFS 34.8 mo) or lorlatinib (CROWN — 5-y PFS 60%) preferred 1L over crizotinib. Adjuvant alectinib 2 y after resection (ALINA).
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-1L, ALGO-NSCLC-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "alk_fusion",
      "value": true
    },
    {
      "finding": "alk_rearrangement",
      "value": "positive"
    },
    {
      "finding": "alk_status",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

Detection: RNA-NGS (preferred for fusion partners) OR FISH break-apart OR IHC (D5F3) screen. Crizotinib effectively obsolete 1L. Lorlatinib has the deepest CNS penetration but most CNS / lipid toxicity; alectinib is the most balanced 1L choice. Sequence: lorlatinib retains activity post-alectinib resistance (G1202R, etc.).

Used By

Algorithms

ALGO-NSCLC-METASTATIC-1L - ALGO-NSCLC-METASTATIC-1L
ALGO-NSCLC-METASTATIC-2L - ALGO-NSCLC-METASTATIC-2L
ALGO-NSCLC-RESECTABLE-PERIOP - ALGO-NSCLC-RESECTABLE-PERIOP