Afatinib is an irreversible kinase inhibitor and binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) to inhibit tyrosine kinase autophosphorylation. This results in a downregulation of ErbB signalling and subsequent inhibition of proliferation of cell lines expressing wild-type EGFR, selected EGFR exon 19 deletion mutations, or exon 21 L858R mutations. It also inhibited in vitro proliferation of cell lines overexpressing HER2. Overall, tumour growth was inhibited.
Afatinib did not effect the QTc interval.
Enzymatic metabolism of afatinib is minimal. Covalent adducts to proteins are the major circulating metabolites.
Most common adverse reactions (≥20%) are diarrhea, rash/dermatitis, acneiform, stomatitis, paronychia, dry skin, decreased appetite, pruritus.