HER2 (ERBB2) activating exon-20 mutation in NSCLC adenocarcinoma — ~2-3% prevalence; dist...

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

ID	`RF-NSCLC-HER2-MUT-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-DESTINYLUNG01-LI-2022` `SRC-DESTINYLUNG02-GOTO-2023` `SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-NCCN-NSCLC-2025`

Red Flag Origin

Definition	HER2 (ERBB2) activating exon-20 mutation in NSCLC adenocarcinoma — ~2-3% prevalence; distinct from HER2 amplification or overexpression. Trastuzumab deruxtecan (T-DXd; DESTINY-Lung01/02 — ORR 49-58%) is the FDA-approved 2L+ targeted ADC. HER2-amp / IHC-only NSCLC has weaker T-DXd response data — kinase-domain mutation is the better predictive biomarker.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "her2_mutation",
      "value": true
    },
    {
      "finding": "erbb2_mutation",
      "value": "positive"
    },
    {
      "finding": "her2_status",
      "value": "mutated"
    }
  ],
  "type": "biomarker"
}

Notes

Detection: NGS panel (PCR misses many in-frame insertions). T-DXd ILD risk ~10-15% in pretreated NSCLC — baseline + serial chest CT, patient education on dyspnea / cough. 1L is still chemo + IO per PD-L1; T-DXd is 2L+. Pyrotinib + chemo investigational in China. Trastuzumab + chemo (TOGA-style) inferior to T-DXd in this molecular subgroup.

Used By

Algorithms

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