The LUX-Lung clinical trial program of afatinib for non-small-cell lung cancer

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.