alexa Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs): a better mousetrap? A review of the clinical evidence.
Oncology

Oncology

Journal of Carcinogenesis & Mutagenesis

Author(s): Ou SH

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Abstract The discovery of activating epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) in 2004 heralded the era of molecular targeted therapy in NSCLC. First-generation small molecule, reversible tyrosine kinase inhibitors (TKIs) of EGFR, gefitinib and erlotinib, had been approved for second- or third-line treatment of NSCLC prior to the knowledge of these mutations. However, resistance to gefitinib and erlotinib invariably develops after prolonged clinical use. Two second-generation irreversible EGFR TKIs, afatinib (BIBW 2992) and dacomitinib (PF-00299804), that can potentially overcome the majority of these resistances are in late stage clinical development. Here I will review the clinical data of EGFR TKIs and discuss the appropriate future role of afatinib and dacomitinib in NSCLC: whether as replacement of erlotinib or gefitinib or only after erlotinib or gefitinib failure and whether different subgroups would benefit from different approaches. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. This article was published in Crit Rev Oncol Hematol and referenced in Journal of Carcinogenesis & Mutagenesis

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