EGFR (ErbB1) mutations define a lung cancer subtype with exquisite sensitivity to EGFR
tyrosine kinase inhibitors (TKIs). While in-frame deletion in exon 19 (Del19) and a point
mutation (L858R) in exon 21 are the two most common sensitizing EGFR mutations in NSCLC,
approximately 10% of EGFR mutation-positive tumors harbor uncommon mutations.
These mutations represent a heterogeneous group of rare molecular alterations (or
combinations) within exons 18-21, whose oncogenicity and sensitivity to EGFR TKIs may vary
and has not been prospectively studied. Recently, a retrospective analysis reported that
overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in
Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M [11]. In
preclinical data, the potency of AZD9291 against uncommon EGFR mutants other than exon 20
insertion mutation was fairly good.
Based on the result, in this study, we try to evaluate the efficacy of AZD9291, the potent
irreversible inhibitor, in NSCLC patients with harboring uncommon EGFR mutations.