Uncommon EGFR AZD9291

Summary

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.

Timeline

Start

2016-01-01

Primary completion

2017-12-31

Completion

2019-07-31

Publications

• Cho JH, Lim SH, An HJ, Kim KH, Park KU, Kang EJ, Choi YH, Ahn MS, Lee MH, Sun JM, Lee SH, Ahn JS, Park K, Ahn MJ. Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09). J Clin Oncol. 2020 Feb 10;38(5):488-495. doi: 10.1200/JCO.19.00931. Epub 2019 Dec 11.

Drugs

Indications