HER2-mutant non-small-cell lung cancer: lines of therapy

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3 standard-of-care settings across 3 lines and 1 biomarker subgroup. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.

Line	All comers
Advanced, first line	1
Second line	1
Special situations	1

Advanced, first line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Advanced, first line	Pembrolizumab plus platinum-pemetrexed as for driver-negative disease; zongertinib or trastuzumab deruxtecan first line only in trials (Beamion LUNG-2, DESTINY-Lung04).	PembrolizumabCarboplatinPemetrexedKEYNOTE-024 & KEYNOTE-189Beamion LUNG-2: A Study to Test Whether Zongertinib (BI 1810631) Helps People With Advanced Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment	NCCN Guidelines: Non-Small Cell Lung Cancer	98

Second line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Advanced, after platinum chemotherapy	Zongertinib (Beamion LUNG-1) or trastuzumab deruxtecan 5.4 mg/kg (DESTINY-Lung02); the other agent at further progression.	ZongertinibBeamion LUNG-1Trastuzumab deruxtecanDESTINY-Lung02SevabertinibSOHO-01Interstitial lung disease (ILD) / pneumonitis	NCCN Guidelines: Non-Small Cell Lung Cancer	97

Special situations

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Brain metastases	Zongertinib and trastuzumab deruxtecan both have intracranial activity; stereotactic radiosurgery for large or symptomatic lesions.	ZongertinibTrastuzumab deruxtecanStereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)Brain metastases (intracranial disease)	NCCN Guidelines: Non-Small Cell Lung Cancer	97

Sequence and caution pairings

CautionApproved

Caution: DXd ADC + agents with pneumonitis risk

Enhertu and its DXd cousins can inflame the lungs; combining them with immunotherapy, radiation, or mTOR inhibitors stacks that risk.

Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.