The epidermal growth factor receptor (EGFR) inhibitors erlotinib, gefitinib, and 
cetuximab have undergone extensive clinical testing and have established 
clinical activity in non-small cell lung cancer and other types of solid tumors. 
A number of newer inhibitors are currently in clinical development with 
different spectra of activity or mechanisms of receptor inhibition. These 
include monoclonal antibodies, such as panitumumab and matuzumab; dual 
inhibitors of EGFR and vascular endothelial growth factor receptor, such as 
ZD6474 and AEE788; inhibitors of multiple EGFR family members, such as 
lapatinib; and irreversible inhibitors, such as canertinib and HKI272. 
Preclinical studies suggest that several of these agents may have activity in 
tumors refractory to erlotinib or gefitinib. Among these agents, ZD6474 has 
undergone the most extensive clinical testing. The antitumor activity of ZD6474 
in these two randomized phase II clinical trials in patients with non-small cell 
lung cancer was felt to be sufficiently promising to warrant phase III clinical 
testing. Several of the other EGFR inhibitors are also undergoing advanced 
clinical testing, either alone or in combination with other agents. EGFR has now 
been validated as a clinically relevant target, and several different types of 
agents inhibiting this receptor are currently in development. Future research 
will be needed to elucidate the role of these agents in patients with EGFR 
inhibitor-naive and EGFR inhibitor-refractory disease, to define the molecular 
characteristics that predict response, and to determine whether these drugs 
should be used in combination with other targeted agents or chemotherapy.