Genomic features, targeted drugs and efficacy of epidermal growth factor receptor (EGFR)-mutant nonsmall cell lung cancers

Genomic featuresFirst- and second-generation EGFR TKIs#RRmPFS monthsSelected third-generation EGFR TKIs overcoming target-mediated resistanceClinical trial phase (study acronym)Total/T790M+ n/nContextRR in T790M+mPFS in T790M+ months
Sensitising kinase domain activating mutations [7]Gefitinib
56–82% [7]9.2–13.1 [7]Osimertinib#I+II [8]
411/411TKI resistant66%9.7–11
Common (90%) del19, exon 21 L858RI [9] (AURA1)60/−TKI naive77%>19
Uncommon (10%) e.g. exon 18 G719X, exon 21 L861QRociletinibI/II [10]
130/51TKI resistant∼30%6.1
HM61713I/II [11]173/76TKI resistant56%7
EGF816I [12]152/152TKI resistant46.9%9.7 m
ASP8273I/II [13] (NA cohort)60/40TKI resistant65%6.7 m
I [14] (Japan cohort)45/15TKI resistant80%

TKI: tyrosine-kinase inhibitor; RR: response rate; mPFS: median progression-free survival; NA: North American. #: European Medicines Agency and US Food and Drug Administration approved; : no longer in clinical development.