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Afatinib: emerging next-generation tyrosine kinase inhibitor for NSCLC

Authors Nelson V, Ziehr J, Agulnik M, Johnson M

Received 1 September 2012

Accepted for publication 10 October 2012

Published 5 March 2013 Volume 2013:6 Pages 135—143

DOI https://doi.org/10.2147/OTT.S23165

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

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Valerie Nelson, Jacqueline Ziehr, Mark Agulnik, Melissa Johnson

Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA

Abstract: The discovery of epidermal growth-factor receptor (EGFR)-activating mutations and the introduction of oral EGFR tyrosine kinase inhibitors (EGFR-TKIs) have expanded the treatment options for patients with non-small cell lung cancer. The first two reversible EGFR-TKIs, erlotinib and gefitinib, are approved for use in the first-line setting in patients with known EGFR-activating mutations and in the second- and third-line settings for all NSCLC patients. These first-generation EGFR-TKIs improve progression-free survival when compared to chemotherapy in patients with EGFR-activating mutations in the first-line setting. However, nearly all patients develop resistance to EGFR-directed agents. There is a need for further therapy options for patients with disease progression after treatment with reversible EGFR-TKIs. Afatinib is an irreversible ErbB family blocker that inhibits EGFR, HER2, and HER4. In vitro and in vivo, afatinib have shown increased inhibition of the common EGFR-activating mutations as well as the T790M resistance mutation when compared to erlotinib and gefitinib. Clinically, afatinib has been evaluated in the LUX-Lung series of trials, with improvement in progression-free survival reported in patients with EGFR-activating mutations in both first- and second-/third-line settings when compared to chemotherapy. Further investigation is needed to determine the precise role that afatinib will play in the treatment of patients with non-small cell lung cancer and EGFR-activating mutations.

Keywords: afatinib, EGFR, irreversible EGFR inhibitor, EGPR-TKIs, LUX lung, resistance mutation, targeted therapy

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