Erlotinib and gefitinib, members of the first generation reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), have became importatnt part of the treatment non-small-cell lung cancer (NSCLC) patients with activating EGFR mutations. However, all patients develop acquired resistence to these agents due to secondary EGFR mutations or other molecular aberrations affecting other signaling pathways.
It was the reason for development of afatinib, an irreversible ErbB family blocker that inhibits broader spectrum of ErbB receptors and confers longer-lasting clinical activity and overcome acquired resistance to firstgeneration inhibitors. Nintedanib is a triple angiokinase inhibitor that potently blocks the primary proangiogenic pathways mediated by vascular endothelial growth factor receptors and also inhibits fibroblast growth factor receptors and platelet-derived growth factor receptors.