Epidermal growth factor receptor inhibitors in development for the treatment of non-small cell lung cancer

The epidermal growth factor receptor (EGER) 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 EGER 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 HK1272, 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 EGER inhibitors are also undergoing advanced clinical testing, either alone, or in combination with other agents. EGER 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 with EGER inhibitor - naive and EGER 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.