Irreversible EGFR Inhibitors in the Treatment of Advanced NSCLC

Title:Irreversible EGFR Inhibitors in the Treatment of Advanced NSCLC

Volume: 20 Issue: 24

Author(s): Paolo Maione, Antonio Rossi, Marianna Bareschino, Paola Claudia Sacco, Clorinda Schettino, Francesca Casaluce, Assunta Sgambato and Cesare Gridelli

Affiliation:

Keywords: Advanced NSCLC, EGFR, irreversible inhibitors, afatinib, PF299804.

Abstract: The epidermal growth factor receptor (EGFR) is among the most important targets in the treatment of advanced non-small cell lung cancer (NSCLC). Erlotinib and gefitinib, two small molecules, are reversible EGFR tyrosine kinase inhibitors (TKIs). Non-small cell lung cancers with EGFR mutations, are characterized by excellent responses when treated with the EGFR-TKIs gefitinib and erlotinib. However, all the patients with tumors harbouring EGFR mutations experience disease progression after a median of 10 to 14 months of treatment with gefitinib or erlotinib. A group of new generation EGFR-TKIs irreversibly inhibit EGFR-TK and represent one of the strategies that may potentially overcome the acquired resistance to gefitinib and erlotinib or achieve better outcomes than reversible inhibitors in the first-line treatment of EGFR mutant lung cancers. Afatinib (BIBW 2992) and PF299804 are the irreversible EGFR-TKIs with the most relevant data in the treatment of advanced NSCLC, as primary EGFR-targeted therapy and after resistance to reversible EGFR-TKIs. However, to date, the role of irreversible EGFR inhibitors remains to be defined.

Cite this article as:

Maione Paolo, Rossi Antonio, Bareschino Marianna, Sacco Claudia Paola, Schettino Clorinda, Casaluce Francesca, Sgambato Assunta and Gridelli Cesare, Irreversible EGFR Inhibitors in the Treatment of Advanced NSCLC, Current Pharmaceutical Design 2014; 20 (24) . https://dx.doi.org/10.2174/13816128113196660764