AUTHOR=Barnes Tristan A. , O’Kane Grainne M. , Vincent Mark David , Leighl Natasha B. 

TITLE=Third-Generation Tyrosine Kinase Inhibitors Targeting Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer

JOURNAL=Frontiers in Oncology

VOLUME=7

YEAR=2017

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2017.00113

DOI=10.3389/fonc.2017.00113

ISSN=2234-943X

ABSTRACT=<p>Sensitizing mutations in the epidermal growth factor receptor (<italic>EGFR</italic>) predict response to <italic>EGFR</italic> tyrosine kinase inhibitors (TKIs) and both first- and second-generation TKIs are available as first-line treatment options in patients with advanced <italic>EGFR</italic>-mutant non-small cell lung cancer. Eventual resistance develops with multiple mechanisms identifiable both upon repeat biopsy and in plasma circulating tumor DNA. The <italic>T790M</italic> gatekeeper mutation is responsible for almost 60% of cases. A number of third-generation TKIs are in clinical development, and osimertinib has been approved by the US Food and Drug Administration for the treatment of patients with <italic>EGFR T790M</italic> mutant lung cancer after failure of initial <italic>EGFR</italic> kinase therapy. Resistance mechanisms are being identified to these novel agents, and the treatment landscape of <italic>EGFR</italic>-mutant lung cancer continues to evolve. The sequence of <italic>EGFR</italic> TKIs may change in the future and combination therapies targeting resistance appear highly promising.</p>