Several EGFR targeted agents have been developed in the field of non-small cell lung cancer (NSCLC) during the last ten years. Most of these are tyrosin-kinase inhibitors (TKIs) and monoclonal antibodies are few.
EGFR-TKIs are categorized to three groups from the points of view of developmental period and the activity for EGFR resistant mutant, T790M. First-generation EGFR-TKIs were developed at first and these inhibit only EGFR-TK reversibly. Gefitinib and erlotinib were included in the category and have been already used in clinical practice. Subsequently, irreversible and pan-HER-TKI (second generation) have been developed. afatinib and dacomitinib are representative agents of this type. These have been conducted several phase III studies for EGFR mutant lung cancer as first-line or lung cancer treated by first-generation EGFR-TKI. Recently, EGFR mutant selective TKIs (third generation) was reported by Wenjun Zhou et al. in NATURE 2009. I hear that one of this type agets is planned to conduct phase I study.
Concerning as EGFR monoclonal antibody, Cetuximab has been evaluated in two phase III studies in patients with advanced NSCLC. One was negative, but the other (FLEX) was a positive phase III study and showed significant prolongation of overall survival in chemotherapy + cetuximab group. Biomarker data in studies using cetuximab consistently showed that mutant KRAS does not predict the resistance of cetuximab in NSCLC.
I would like to discuss the position of EGFR-TKI & EGFR monoclonal antibody in the treatment of advanced NSCLC in this session.