Back to Journals » The Application of Clinical Genetics » Volume 10

Treating EGFR mutation resistance in non-small cell lung cancer – role of osimertinib

Authors Mazza V, Cappuzzo F

Received 8 February 2017

Accepted for publication 6 May 2017

Published 26 July 2017 Volume 2017:10 Pages 49—56

DOI https://doi.org/10.2147/TACG.S103471

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Martin H. Maurer


Valentina Mazza,1 Federico Cappuzzo1,2

1Department of Oncology-Hematology, 2Department of Medical Oncology, AUSL Romagna, Ravenna, Italy

Abstract: The discovery of mutations in EGFR significantly changed the treatment paradigm of patients with EGFR-mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to EGFR-wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs. The most common mechanism of acquired resistance to EGFR-TKIs is the development of a second mutation in exon 20 of EGFR (T790M). Osimertinib is a third-generation EGFR-TKI designed for overcoming T790M-mediated resistance. Based on the results of efficacy and tolerability of Phase II and Phase III studies, osimertinib has been approved for treatment of advanced EGFRT790M+ mutation NSCLC following progression on a prior EGFR-TKI. Occurrence of acquired resistance to osimertinib represents an urgent need for additional strategies including combination with other agents, such as other targeted therapies or checkpoint inhibitors, or development of new and more potent compounds.

Keywords: EGFR-mutant non-small-cell Lung cancer, acquired resistance, T790M mutation, third generation EGFR-TKI, osimertinib

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]