HER2-mutant non-small-cell lung cancer: the decisions you may face

• KEYNOTE-024 & KEYNOTE-189Phase 3NCT021427382016921 peopleevidence 95
  Tests Pembrolizumab
  First-line metastatic NSCLC without EGFR/ALK: pembrolizumab alone (PD-L1 TPS ≥50%, KEYNOTE-024) or pembrolizumab + platinum-pemetrexed (any PD-L1, non-squamous, KEYNOTE-189)
  ▸Show survival figures (1)

  Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • 5-year OS 31.9% vs 16.3% (024); 19.4% vs 11.3% (189).
  KEYNOTE-024: overall survival at 5 years, PD-L1 ≥50% (%): Pembrolizumab 31.9 (n=154) vs Chemotherapy 16.3 (n=151) · HR 0.62 · source
• Beamion 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 TreatmentPhase 3NCT06151574428 peopleevidence 48
  Tests Pembrolizumab, Carboplatin, Pemetrexed
  Beamion LUNG 2: A Phase III, Open-label, Randomized, Active-controlled, Multi-centre Trial Evaluating Orally Administered Zongertinib (BI 1810631) Compared With Standard of Care as First-line Treatment in Patients With Unresectable, Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Harbouring HER2 Tyrosine Kinase Domain Mutations

  No headline result recorded yet.

1. Between Pembrolizumab, Carboplatin and Pemetrexed, which do you recommend for me, and what about my case would make you choose differently?
   Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
   Why: The aim shapes how much side effect and disruption is worth accepting.
3. How closely do I match the people in KEYNOTE-024 & KEYNOTE-189 and Beamion 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, and does that change what the results mean for me?
   Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
4. Which side effects of Pembrolizumab are most likely for me, which are reversible, and which would make us stop?
   Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
5. What happens if I delay, or decline this step for now? Is the decision reversible?
   Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
6. Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?
   Why: Departures from guidelines are sometimes right for an individual; they should be explained.
7. For my situation (advanced, first line), which of the standard options do you recommend and why?
   Why: Guideline options include: Pembrolizumab plus platinum-pemetrexed as for driver-negative disease; zongertinib or trastuzumab deruxtecan first line only in trials (Beamion LUNG-2, DESTINY-Lung04).
8. Am I a candidate for Pembrolizumab, Carboplatin, Pemetrexed, and what side effects should I expect?
   Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
9. How do the results of KEYNOTE-024 & KEYNOTE-189 and Beamion 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 apply to someone like me?
   Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

• Beamion LUNG-1Phase 1/2NCT048868042025evidence 46
  Tests Zongertinib, Trastuzumab deruxtecan
  Previously treated advanced HER2 (ERBB2)-mutant non-small-cell lung cancer: zongertinib, an oral HER2-selective tyrosine kinase inhibitor, in cohorts by prior HER2-directed therapy

  Confirmed response rate 71% in 75 previously treated patients naive to HER2-directed therapy; 48% after a HER2 antibody-drug conjugate; FDA accelerated approval August 2025.

  Confirmed objective response rate (%): Zongertinib, previously treated, no prior HER2-directed therapy 71 (n=75) vs Zongertinib after a HER2 antibody-drug conjugate 48 (n=31) · source
• DESTINY-Lung02Phase 2NCT046442372023152 peopleevidence 64
  Tests Trastuzumab deruxtecan
  Previously treated metastatic HER2 (ERBB2)-mutant non-small-cell lung cancer: trastuzumab deruxtecan 5.4 mg/kg versus 6.4 mg/kg

  Confirmed response rate 49.0% (5.4 mg/kg) vs 56.0% (6.4 mg/kg); interstitial lung disease 12.9% vs 28.0%.

  Confirmed objective response rate (%): Trastuzumab deruxtecan 5.4 mg/kg 49 (n=102) vs Trastuzumab deruxtecan 6.4 mg/kg 56 (n=50) · source
• SOHO-01Phase 1/2NCT050991722025407 peopleevidence 49
  Tests Sevabertinib
  HER2-mutant NSCLC, previously treated and treatment-naive: sevabertinib single arm

  ORR ~64%; accelerated approval Nov 2025.

  Objective response rate, HER2-mutant NSCLC after platinum (Cohort D) (%): Sevabertinib 20 mg 70.5 · source

1. Between Zongertinib, Trastuzumab deruxtecan and Sevabertinib, which do you recommend for me, and what about my case would make you choose differently?
   Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
   Why: The aim shapes how much side effect and disruption is worth accepting.
3. How closely do I match the people in Beamion LUNG-1 and DESTINY-Lung02, and does that change what the results mean for me?
   Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
4. Which side effects of Trastuzumab deruxtecan are most likely for me, which are reversible, and which would make us stop?
   Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
5. What happens if I delay, or decline this step for now? Is the decision reversible?
   Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
6. Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?
   Why: Departures from guidelines are sometimes right for an individual; they should be explained.
7. For my situation (advanced, after platinum chemotherapy), which of the standard options do you recommend and why?
   Why: Guideline options include: Zongertinib (Beamion LUNG-1) or trastuzumab deruxtecan 5.4 mg/kg (DESTINY-Lung02); the other agent at further progression.
8. Am I a candidate for Zongertinib, Trastuzumab deruxtecan, Sevabertinib, and what side effects should I expect?
   Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
9. How do the results of Beamion LUNG-1 and DESTINY-Lung02 apply to someone like me?
   Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

1. Between Zongertinib, Trastuzumab deruxtecan and Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS), which do you recommend for me, and what about my case would make you choose differently?
   Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
   Why: The aim shapes how much side effect and disruption is worth accepting.
3. Which side effects of Trastuzumab deruxtecan are most likely for me, which are reversible, and which would make us stop?
   Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
4. What happens if I delay, or decline this step for now? Is the decision reversible?
   Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
5. Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?
   Why: Departures from guidelines are sometimes right for an individual; they should be explained.
6. For my situation (brain metastases), which of the standard options do you recommend and why?
   Why: Guideline options include: Zongertinib and trastuzumab deruxtecan both have intracranial activity; stereotactic radiosurgery for large or symptomatic lesions.
7. Am I a candidate for Zongertinib, Trastuzumab deruxtecan, and what side effects should I expect?
   Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Add these to your appointment list, or take the full question set for this cancer.