RET fusion (KIF5B-RET, CCDC6-RET, others) — ~1-2% of NSCLC adenocarcinoma. Selpercatinib...

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

ID	`RF-NSCLC-RET-FUSION-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-ARROW` `SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-LIBRETTO001-DRILON-2020` `SRC-NCCN-NSCLC-2025`

Red Flag Origin

Definition	RET fusion (KIF5B-RET, CCDC6-RET, others) — ~1-2% of NSCLC adenocarcinoma. Selpercatinib (LIBRETTO-001 — ORR 85% TKI-naive) and pralsetinib (ARROW) are FDA-approved selective RET-TKIs; preferred 1L over multikinase (cabo, vandetanib).
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-1L, ALGO-NSCLC-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "ret_fusion",
      "value": true
    },
    {
      "finding": "ret_rearrangement",
      "value": "positive"
    },
    {
      "finding": "ret_status",
      "value": "fusion_positive"
    }
  ],
  "type": "biomarker"
}

Notes

RET fusions are best detected by RNA-NGS (DNA-NGS may miss some rearrangements with intronic breakpoints). LIBRETTO-431 confirmed selpercatinib superiority over chemo + pembro in 1L (mPFS 24.8 vs 11.2 mo). Selpercatinib has CNS activity. Hypertension + LFT elevation + QTc prolongation are class effects.

Used By

Algorithms

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

Red flag

RF-MTC-RET-MUTANT - RET proto-oncogene activating mutation (somatic or germline) in advanced or metastatic me...