Original Study Association Between EGFR T790M Status and Progression Patterns During Initial EGFR-TKI Treatment in Patients Harboring EGFR Mutation Yuko Oya, 1 Tatsuya Yoshida, 1 Hiroaki Kuroda, 2 Junichi Shimizu, 1 Yoshitsugu Horio, 1 Yukinori Sakao, 2 Yoshitaka Inaba, 3 Toyoaki Hida, 1 Yasushi Yatabe 4 Abstract Progression patterns at the time of resistance to the initial epidermal growth factor receptor (EFGR)-tyrosine kinase inhibitors are clinically heterogeneous. The associations between progression patterns and the EGFR T790M mutation have not been elucidated. In this study, we found that solitary lesion progression at the time of failure of the initial treatment with EGFR-tyrosine kinase inhibitors is significantly associated with a T790M mutation status by multivariate analysis. Background: Emergence of the T790M point mutation in exon 20 of the epidermal growth factor receptor (EGFR) is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The aim of this study was to investigate the association between T790M mutation status and the progression patterns during EGFR-TKI treatment. Methods: We reviewed 181 patients with advanced nonesmall-cell lung cancer harboring EGFR muta- tion, who were evaluated for T790M mutation status after initial EGFR-TKI failure (gefitinib, erlotinib, or afatinib). We retrospectively investigated the patient characteristics, initial EGFR-TKI response, T790M mutation status, subse- quent treatment after initial EGFR-TKIs, timing of re-biopsy, and progression patterns during the EGFR-TKI treatment. Results: After the resistance to the EGFR-TKIs, the T790M mutation was identified in 87 (48%) of 181 patients. Seventy-three (40%) patients had solitary lesion progression, and 108 (60%) had multiple lesion progression during the initial EGFR-TKI treatment. The prevalence of the T790M mutation was significantly greater in patients with solitary lesion progression than those with multiple lesion progression (58% vs. 24%; P < .0001). The overall response rate and progression-free survival on initial EGFR-TKIs were significantly better in patients who acquired T790M after failure of EGFR-TKIs than those without T790M (overall response rate, 80% vs. 60%; P ¼ .0033 and progression-free survival, 11.4 vs. 9.3 months; P ¼ .0050). The multivariate analysis showed that gender, initial EGFR-TKI response, and progression patterns were significantly associated with T790M mutation status. Discussion: The progression patterns during initial EGFR-TKIs and initial EGFR-TKI response are associated with the T790M mutation. Clinical Lung Cancer, Vol. 18, No. 6, 698-705 ª 2017 Elsevier Inc. All rights reserved. Keywords: EGFR T790M mutation, Epidermal growth factor receptor, Epidermal growth factor receptor-tyrosine kinase in- hibitors, Nonesmall-cell lung cancer, Progression patterns Introduction Somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are the most reliable predictors for the efficacy of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in patients with nonesmall-cell lung cancer (NSCLC). In randomized phase III trials, treatment of patients with NSCLC who had an activating EGFR mutation with EGFR-TKIs was associated with a longer progression-free survival (PFS) and 1 Department of Thoracic Oncology 2 Department of Thoracic Surgery 3 Department of Diagnostic and Interventional Radiology 4 Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Aichi, Japan Submitted: Feb 12, 2017; Revised: May 1, 2017; Accepted: May 2, 2017; Epub: May 10, 2017 Address for correspondence: Tatsuya Yoshida, MD, PhD, Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan E-mail contact: t.yoshida@aichi-cc.jp 698 - Clinical Lung Cancer November 2017 1525-7304/$ - see frontmatter ª 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cllc.2017.05.004