Inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase: similarity and differences

Tyrosine kinase inhibitors (TKI) of EGFR are used in advanced non-small cell Lung cancer (NSCLC) in 2(nd) and 3(rd) line, and for gefitinib in first line in case of EGFR mutations. These drugs are particularly active in presence of these mutations, with response rate around 60-70 %. Pharmacological data suggest an equivalent effect of erlotinib and gefitinib. One phase II study has directly compared the two drugs in 2(nd) line, with a non significant advantage for gefitinib in term of response and progression-free survival. However, skin tolerance profile was statistically better with gefitinib. Indirect comparisons between erlotinib and gefitinib in the phase III trials vs chemotherapy 1(st) line have to be interpreted, with caution and take under consideration the impact of the chemotherapy arm on the Hazard Ratio for Progression-free and overall survival. However, response rates seem to be equivalent. Cohort and phase IV studies have shown no significant difference for response and survival, and a similar tolerance profile. (C) 2011 Elsevier Masson SAS. bus droits reserves.