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World J Clin Oncol. Oct 10, 2014; 5(4): 646-659
Published online Oct 10, 2014. doi: 10.5306/wjco.v5.i4.646
Epidermal growth factor receptor tyrosine kinase inhibitors for non-small cell lung cancer
Kazuhiro Asami, Shinji Atagi
Kazuhiro Asami, Shinji Atagi, Department of Clinical Oncology, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai City, Osaka 591-8555, Japan
Author contributions: Asami K and Atagi S both contributed to this paper.
Correspondence to: Kazuhiro Asami, MD, Department of Clinical Oncology, National Hospital Organization Kinki-chuo Chest Medical Center, 1180 Nagasone-cho Kita-ku, Sakai City, Osaka 591-8555, Japan. kazu.taizo@nifty.com
Telephone: +81-72-2523021 Fax: +81-72-2511372
Received: December 22, 2013
Revised: April 22, 2014
Accepted: May 15, 2014
Published online: October 10, 2014
Processing time: 215 Days and 8.7 Hours
Abstract

First-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib and erlotinib, have proven to be highly effective agents for advanced non-small cell lung cancer (NSCLC) in patients harboring an activating EGFR mutation such as the exon 19 deletion mutation and L858R. Although those reversible small molecular targeted agents provide a significant response and survival benefit, all responders eventually acquire resistance. Second-generation EGFR-targeting agents, such as irreversible EGFR/HER2 tyrosine kinase inhibitors and pan-HER TKIs, may improve survival further and be useful for patients who acquired resistance to first-generation EGFR-TKIs. This review discusses novel therapeutic strategies for EGFR-mutated advanced NSCLC using first- and second-generation EGFR-TKIs.

Keywords: Epidermal growth factor receptor mutation; Epidermal growth factor receptor tyrosine kinase inhibitors; Non-small cell lung cancer; Secondary resistance

Core tip: Although gefitinib and erlotinib provide a significant response and survival benefit, all responders eventually acquire resistance. Second-generation epidermal growth factor receptor (EGFR)-targeting agents, such as afatinib and dacomitinib, may improve survival further and be useful for patients who acquired resistance to first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). This review discusses novel therapeutic strategies for EGFR-mutated advanced non-small cell lung cancer using first- and second-generation EGFR-TKIs.