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Afatinib for the treatment of metastatic non-small cell lung cancer

Authors Joshi M, Rizvi SM, Belani CP

Received 1 December 2014

Accepted for publication 14 January 2015

Published 19 February 2015 Volume 2015:7 Pages 75—82

DOI https://doi.org/10.2147/CMAR.S51808

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Kenan Onel

Video abstract presented by Monika Joshi

Views: 288

Monika Joshi, Syed M Rizvi, Chandra P Belani

Penn State Milton S Hershey Medical Center, Department of Medicine, Division of Hematology-Oncology, Hershey, PA, USA

Abstract: Targeting the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC) harboring sensitizing mutations in the tyrosine kinase (TKI) domain has led to a significant change in the management of this disease. The classic or sensitizing mutations are G719X mutation in exon 18, in-frame deletions or insertion of exon 19, L858R or L861Q mutation in exon 21. Approximately 90% of these mutations are exon 19 deletion or exon 21 L858R point mutation. Gefitinib and erlotinib are reversible first-generation inhibitors of mutant EGFR, and treatment with these agents in the first-line setting has demonstrated a progression-free survival of 9.5–13.7 months. However, the majority of these patients ultimately develop resistance to these drugs. Afatinib is an irreversible pan-ErbB inhibitor that was developed to circumvent the problem of resistance to first-generation TKIs. The LUX-Lung studies have evaluated the efficacy and toxicities of afatinib in treatment-naïve and refractory NSCLC patients. The promising results of some of these trials led to approval of afatinib by the US Food and Drug Administration for patients with advanced NSCLC and EGFR exon 19 deletions or exon 21 (L858R) substitution mutations. Afatinib causes toxicities similar to those of the first-generation EGFR TKIs, such as diarrhea, rash, acne, and stomatitis, and overall is well tolerated. This article focuses on the clinical studies of afatinib in patients with NSCLC.

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


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