Anti-EGFR monoclonal antibodies in the treatment of non-small cell lung cancer

In summary, targeted drugs, primarily the EGFR inhibitors, have added new effective agents to the therapeutic armamentarium for NSCLC. Qualitative and quantitative survival benefit has been demonstrated with small molecules TKIs, but also anti-EGFR monoclonal antibodies, even though in an earlier stage of clinical investigation, have demonstrated promising activity that warrants further studies of these agents. Mutations in the ATP-binding site, that have been consistently associated with clinical response to TKIs [11], do not seem to predict response to anti-EGFR therapy using monoclonal antibodies such as cetuximab [4, 12]. Moreover, it has recently been reported that two patients responded to gefitinib after failure of several chemotherapy regimens and cetuximab [15]. Taken together, these findings could suggest that monoclonal antibodies and TKIs have different mechanisms of action and might be effectively combined in order to broaden their spectrum of activity.