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First-line treatment of EGFR-mutant non-small-cell lung cancer: the role of erlotinib and other tyrosine kinase inhibitors

Authors Nguyen KS, Neal JW

Received 16 June 2012

Accepted for publication 13 August 2012

Published 25 September 2012 Volume 2012:6 Pages 337—345

DOI https://dx.doi.org/10.2147/BTT.S26558

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Kim-Son H Nguyen, Joel W Neal

Stanford Cancer Institute, Stanford University, Stanford, CA, USA

Abstract: Epidermal growth factor–receptor tyrosine kinase inhibitors (EGFR TKIs) were initially established as second- or third-line treatment of advanced non-small-cell lung cancer (NSCLC). Subsequent studies, including IPASS, OPTIMAL, and EURTAC, have demonstrated that these TKIs are effective first-line therapeutic options in patients with tumors harboring activating mutations in the EGFR gene. The TKIs are better tolerated than conventional chemotherapy, with frequent yet mild side effects such as rash and diarrhea, and rarely interstitial lung disease. Because most patients on TKIs develop resistance due to a variety of mechanisms, the use of TKIs in the acquired-resistance setting and in the setting of earlier-staged cancers is being extensively studied. Here we review the major trials leading to the established use of EGFR TKIs in NSCLC, followed by discussion of recently completed and ongoing trials using the next-generation EGFR inhibitor afatinib.

Keywords: epidermal growth factor receptor, non-small-cell lung cancer, tyrosine kinase inhibitor, epidermal growth factor–receptor mutation

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