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Review
. 2016;16(4):383-90.
doi: 10.1586/14737140.2016.1162103. Epub 2016 Mar 21.

The safety and efficacy of osimertinib for the treatment of EGFR T790M mutation positive non-small-cell lung cancer

Xin Gao  1 , Xiuning Le  1 , Daniel B Costa  1
Affiliations
Review

The safety and efficacy of osimertinib for the treatment of EGFR T790M mutation positive non-small-cell lung cancer

Xin Gao et al. Expert Rev Anticancer Ther. 2016.

Abstract

First- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the evidence-based first-line treatment for metastatic non-small-cell lung cancers (NSCLCs) that harbor sensitizing EGFR mutations (i.e. exon 19 deletions or L858R). However, acquired resistance to EGFR TKI monotherapy occurs invariably within a median time frame of one year. The most common form of biological resistance is through the selection of tumor clones harboring the EGFR T790M mutation, present in >50% of repeat biopsies. The presence of the EGFR T790M mutation negates the inhibitory activity of gefitinib, erlotinib, and afatinib. A novel class of third-generation EGFR TKIs has been identified by probing a series of covalent pyrimidine EGFR inhibitors that bind to amino-acid residue C797 of EGFR and preferentially inhibit mutant forms of EGFR versus the wild-type receptor. We review the rapid clinical development and approval of the third-generation EGFR TKI osimertinib for treatment of NSCLCs with EGFR-T790M.

Keywords: EGFR; T790M; TKI; adenocarcinoma; kinase inhibitor; lung cancer; mutation; osimertinib; resistance.

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Conflict of interest statement

Competing interests disclosure

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1
Figure 1
Chemical structures and basic information on selected preclinical and clinical third-generation EGFR inhibitors based on data deposited on the PubChem Compound and Substance databases [62]. Clinical responses reflect data from references [42] and [46]. Activity is grade from minimum (+) to maximum (+++++).
Figure 2
Figure 2
Treatment algorithm for patients with EGFR-mutated advanced NSCLC.
See this image and copyright information in PMC

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