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The LUX-Lung clinical trial program of afatinib for non-small-cell lung cancer
1Division of Medical Oncology, Azienda Ospedaliera S Maria della Misericordia, via Dottori, 1, Perugia 06156, Italy.
Abstract:
Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) represents a distinct disease entity whose molecular phenotype predicts exquisite sensitivity to the reversible EGFR-tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib. However, primary or acquired resistance to these agents remains a major clinical problem. Afatinib is a novel dual irreversible EGFR/HER2 TKI that has been shown in preclinical studies to potentially prevent, delay or overcome resistance to reversible EGFR-TKIs. On this basis, the LUX-Lung clinical trial program has been recently launched for testing this molecule in advanced NSCLC patients. Notably, early results from the randomized LUX-Lung 1 trial indicate that afatinib significantly prolongs progression-free survival compared with placebo in pretreated patients with clinically acquired resistance to gefitinib or erlotinib. On the other hand, the LUX-Lung 2 trial shows that afatinib is highly active in the EGFR-mutant subgroup of patients. While these preliminary data open a new exciting scenario for the future development of anti-EGFR therapies in NSCLC, ongoing afatinib trials will definitively establish a role for this molecule in the treatment of advanced NSCLC.
Insights
Afatinib, an irreversible EGFR/HER2 inhibitor, shows promise in treating advanced non-small-cell lung cancer (NSCLC). Early trials suggest it may overcome resistance to other EGFR-tyrosine kinase inhibitors (TKIs) and benefit EGFR-mutant NSCLC patients.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) is sensitive to reversible EGFR-tyrosine kinase inhibitors (TKIs).
- Primary or acquired resistance to these TKIs presents a significant clinical challenge.
- Afatinib, a novel irreversible EGFR/HER2 TKI, has shown potential in preclinical studies to overcome TKI resistance.
Purpose of the Study:
- To evaluate the efficacy of afatinib in advanced NSCLC patients, particularly those with EGFR mutations or resistance to prior therapies.
- To investigate afatinib's potential to prevent, delay, or overcome resistance to reversible EGFR-TKIs.
Main Methods:
- The LUX-Lung clinical trial program was initiated to test afatinib in advanced NSCLC.
- LUX-Lung 1: A randomized trial in pretreated patients with acquired resistance to gefitinib or erlotinib.
- LUX-Lung 2: Investigated afatinib in the EGFR-mutant subgroup of NSCLC patients.
Main Results:
- LUX-Lung 1: Afatinib significantly prolonged progression-free survival compared to placebo in patients resistant to gefitinib or erlotinib.
- LUX-Lung 2: Afatinib demonstrated high activity in the EGFR-mutant NSCLC subgroup.
Conclusions:
- Preliminary data suggest afatinib is a promising therapeutic option for advanced NSCLC.
- Afatinib may offer a new strategy to overcome resistance to existing EGFR-targeted therapies.
- Ongoing trials are crucial to definitively establish afatinib's role in NSCLC treatment.
