TY - JOUR
T1 - Can we define the optimal sequence of epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of epidermal growth factor receptor-mutant nonsmall cell lung cancer?
AU - Sun, Jong Mu
AU - Park, Keunchil
N1 - Publisher Copyright:
© 2017 Wolters Kluwer Health, Inc.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Purpose of review The most common mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is acquisition of the T790M gatekeeper mutation. Third-generation EGFR TKIs irreversibly inhibit EGFR mutants (EGFRm), especially T790M, while sparing wild-type EGFR. There are several third-generation EGFR TKIs under development, including osimertinib, CO-1686 (rociletinib), HM61713 (olmutinib), ASP8273, and EGF816. These third-generation EGFR TKIs have shown promising efficacy with favorable toxicity profiles in the management of advanced nonsmall cell lung cancer (NSCLC) with an acquired T790M mutation (EGFRT790M). In the present review, we will discuss the evolving treatment landscape of EGFRm NSCLC. Recent findings The LUX-Lung 7 study demonstrated superior progression-free survival, time-to-treatment failure, and objective response rate with afatinib versus gefitinib, but no significant overall survival improvement in TKI-naïve EGFRm NSCLC patients. In EGFRm NSCLC patients harboring T790M after treatment with first-generation or second-generation EGFR TKIs, third-generation EGFR TKIs showed robust efficacy with tolerable toxicity. The updated results of phase I studies have demonstrated encouraging activity of first-line osimertinib in patients with EGFRm NSCLC. Summary Following progression with first-generation or second-generation EGFR TKIs, osimertinib was recently approved for the treatment of EGFRT790M NSCLC. Encouraging early results with osimertinib have sparked interest in first-line treatment of EGFRm NSCLC, and head-to-head comparison studies of third-generation versus first-generation EGFR TKIs are being developed.
AB - Purpose of review The most common mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is acquisition of the T790M gatekeeper mutation. Third-generation EGFR TKIs irreversibly inhibit EGFR mutants (EGFRm), especially T790M, while sparing wild-type EGFR. There are several third-generation EGFR TKIs under development, including osimertinib, CO-1686 (rociletinib), HM61713 (olmutinib), ASP8273, and EGF816. These third-generation EGFR TKIs have shown promising efficacy with favorable toxicity profiles in the management of advanced nonsmall cell lung cancer (NSCLC) with an acquired T790M mutation (EGFRT790M). In the present review, we will discuss the evolving treatment landscape of EGFRm NSCLC. Recent findings The LUX-Lung 7 study demonstrated superior progression-free survival, time-to-treatment failure, and objective response rate with afatinib versus gefitinib, but no significant overall survival improvement in TKI-naïve EGFRm NSCLC patients. In EGFRm NSCLC patients harboring T790M after treatment with first-generation or second-generation EGFR TKIs, third-generation EGFR TKIs showed robust efficacy with tolerable toxicity. The updated results of phase I studies have demonstrated encouraging activity of first-line osimertinib in patients with EGFRm NSCLC. Summary Following progression with first-generation or second-generation EGFR TKIs, osimertinib was recently approved for the treatment of EGFRT790M NSCLC. Encouraging early results with osimertinib have sparked interest in first-line treatment of EGFRm NSCLC, and head-to-head comparison studies of third-generation versus first-generation EGFR TKIs are being developed.
KW - epidermal growth factor receptor mutation
KW - nonsmall cell lung cancer
KW - sequence
KW - T790M
KW - third-generation epidermal growth factor receptor tyrosine kinase inhibitor
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U2 - 10.1097/CCO.0000000000000350
DO - 10.1097/CCO.0000000000000350
M3 - Review article
C2 - 28085680
AN - SCOPUS:85010905730
SN - 1040-8746
VL - 29
SP - 89
EP - 96
JO - Current opinion in oncology
JF - Current opinion in oncology
IS - 2
ER -