Since the results of IDEAL-1 (1) and the approval of gefitinib, a first-class epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), 15 years have passed. The efficacy of first-line EGFR-TKI, gefitinib (2,3), erlotinib (4), icotinib (5), and second-line EGFR-TKI, afatinib (6), is 6.3-11.0 months for median progression-free survival (PFS), 19.4-28.2 months for median overall survival (OS), and 44.1-73.7% for the response rates, respectively.Osimertinib mesylate (AZD9291, Tagrisso TM ) is an oral mono-anilino-pyrimidine small molecule that is promising for the treatment of mutant-selective EGFR-TKI. In particular, osimertinib is anticipated to exhibit potent activity against advanced non-small cell lung cancer (NSCLC) harboring the EGFR mutation, T790M, indicating resistance to EGFR-TKI as the breakthrough therapy (7). Half of the resistance to EGFR-TKI occurs via acquired resistance associated with exon 20 T790M. In the standard of care, cytotoxic chemotherapy has been applied with a response rate of 30-40% and median PFS of four to seven months as a first-line cytotoxic chemotherapy or response rate of 10-20% and median PFS of two months as second-line (8) treatment until the advent of osimertinib. Medical oncologists have been anticipated to respond by following later lines of chemotherapy as a re-challenge of EGFR-TKI with response rates of 4.9-8.2% (9) or the second-generation EGFR-TKI, afatinib, following the failure of first-generation EGFR-TKIs (10). In a secondline setting after the failure of EGFR-TKI harboring exon 20 T790M, osimertinib was confirmatory improved PFS compared to the platinum-pemetrexed combination administered in the phase III trial (AURA3 trial) conducted by Mok et al. (11). In the AURA3, 419 patients with T790M-positive NSCLC were randomized to receive either 80 mg osimertinib once daily, or chemotherapy [pemetrexed 500 mg/m 2 every three weeks plus platinum (carboplatin targeting an area under the curve 5 or 75 mg/m 2 of cisplatin)]. The median PFS as the primary endpoint was successfully completed at 10.1 months for the osimertinib arm and over 4.4 months for the chemotherapy arm [hazard ratio (HR): 0.30; 95% confidence interval (CI): 0.23-0.41; P<0.001]. The objective response rate (ORR) was 71% vs. 31% for osimertinib and chemotherapy, respectively (odds ratio: 5.39; 95% CI: 3.47-8.4; P<0.001). In this trial, the patients exhibited CNS metastasis at 8.5 months for the PFS of osimertinib compared to 4.2 months for those receiving chemotherapy (HR: 0.32; 95% CI: 0.21-0.49). Among the patients without central nervous system (CNS) metastasis, the PFS was 10.8 months for osimertinib and 5.6 months for chemotherapy (HR: 0.40; 95% CI: 0.29-0.55). In addition, there is promising data indicating that osimertinib is preferable to the penetration of the CNS over other EGFR-TKIs using an animal J Thorac Dis 2017;9(3):470-473 jtd.amegroups.com model (12). In the BLOOM study (NCT02228369), 20 patients with leptomeningeal metastasis exhibiting an EGFR mutation were treated with 16...