@article{ATM17080,
author = {Giannis Mountzios},
title = {Making progress in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer by surpassing resistance: third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs)},
journal = {Annals of Translational Medicine},
volume = {6},
number = {8},
year = {2017},
keywords = {},
abstract = {Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) represent the standard of care for advanced non-small cell lung cancer (NSCLC) patients whose tumours harbor an activating EGFR mutation. Unfortunately, resistance to first- and second-generation EGFR-TKIs inevitably occurs in all patients with EGFR-mutant disease approximately within a year of treatment. At least half of these cases are attributed to the emergence of a secondary mutation in exon 20 of the EGFR gene, namely the T790M mutation. Third-generation EGFR-TKIs, including osimertinib and rociletinib, target this epigenic mutation, thus re-sensitizing cancer cells to EGFR-TKI inhibition. Osimertinib to date represents the standard of care in EGFR-mutant tumors after failure of first-line EGFR-TKIs by over-performing platinum-based chemotherapy in the recently reported AURA-3 randomized phase III clinical trial. The aim of this review is to describe the different treatment strategies that have been developed to reverse resistance to first- and second-line EGFR-TKIs, the corresponding mechanisms of resistance and the development of novel-generation EGFR-TKIs. We also discuss the challenge posed by the implementation of third-generation EGFR-TKIs earlier in the course of the disease in first-line treatment of EGFR-mutant NSCLC.},
issn = {2305-5847}, url = {https://atm.amegroups.org/article/view/17080}
}