The epidermal growth factor receptor (EGFR) is among the most important targets in the treatment of advanced non-small cell
lung cancer (NSCLC). Erlotinib and gefitinib, two small molecules, are reversible EGFR tyrosine kinase inhibitors (TKIs). Non-small
cell lung cancers with EGFR mutations, are characterized by excellent responses when treated with the EGFR-TKIs gefitinib and erlotinib.
However, all the patients with tumors harbouring EGFR mutations experience disease progression after a median of 10 to 14 months
of treatment with gefitinib or erlotinib. A group of new generation EGFR-TKIs irreversibly inhibit EGFR-TK and represent one of the
strategies that may potentially overcome the acquired resistance to gefitinib and erlotinib or achieve better outcomes than reversible inhibitors
in the first-line treatment of EGFR mutant lung cancers. Afatinib (BIBW 2992) and PF299804 are the irreversible EGFR-TKIs
with the most relevant data in the treatment of advanced NSCLC, as primary EGFR-targeted therapy and after resistance to reversible
EGFR-TKIs. However, to date, the role of irreversible EGFR inhibitors remains to be defined.