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.