Loss of T790M mutation is associated with early progression to osimertinib in Chinese patients with advanced NSCLC who are harboring EGFR T790M. (February 2019)

• Record Type: Journal Article
• Authors: Zhao, Sha; Li, Xuefei; Zhao, Chao; Jiang, Tao; Jia, Yijun; Shi, Jinpeng; He, Yayi; Li, Jiayu; Zhou, Fei; Gao, Guanghui; Li, Wei; Chen, Xiaoxia; Su, Chunxia; Ren, Shengxiang; Zhou, Caicun
• Is Part Of: Lung cancer. Volume 128(2019)
• Page Start: 33
• Page End: 39
• Publication Date: 2019-02
• Subjects: Non-small cell lung cancer -- Osimertinib -- Loss of T790M mutation -- Early progression; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2018.12.010
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: We reviewed the post-osimertinib T790 M mutational status in a Chinese NSCLC patient cohort. Loss of T790 M is prevalent on resistance to osimertinib in T790M-positive NSCLC patients. Loss of T790 M at osimertinib resistance correlated to early progression and worse survival. Abstract: Background: Osimertinib demonstrates superior efficacy in patients with non-small cell lung cancer (NSCLC) who acquired EGFR T790M mutation as resistant mechanism to upfront EGFR tyrosine kinase inhibitors (TKIs). Not all the T790M-positive tumors are homogeneously sensitive to osimertinib, however, and the duration of response often varies. Previous studies suggest that loss of T790 M at osimertinib resistance is correlated with shortened survival benefit of osimertinib. The aim of this study is to investigate the prevalence of T790 M loss after progression to osimertinib in Chinese patients with NSCLC harboring EGFR T790 M mutation and to compare their clinical outcomes and characteristics when stratified by T790 M mutational status at osimertinib resistance. Patients and methods: All patients with a secondary T790 M mutation after progression to prior-line EGFR TKIs and received single-agent osimertinib were reviewed. The patients who were reassessed for T790 M mutation post-osimertinib resistance were included in final analysis. Detailed clinicopathologic characteristics and response data were collected. Results: Of the patients with confirmed T790 M mutation as acquired resistance to early-generation EGFR TKIs and subsequently received single-agent osimertinib, 84 patients experienced clinical progression after osimertinib treatment and were eligible for analysis. Among them, 31 patients underwent repeated T790 M mutation testing on osimertinib resistance. Sixteen patients had maintained T790 M mutation, whereas 15 patients lost T790 M at resistance. Loss of T790 M at resistance was remarkably correlated with shorter duration of response to osimertinib ( P = 0.0005). Furthermore, the overall survival after osimertinib treatment was also decreased in T790M-loss group (P=0.021). The objective response rates were comparable between T790M-maintain and T790M-loss group (31.3% and 26.7%, respectively). In multivariate analysis, loss of T790M remained statistically associated with early progression to osimertinib. Conclusion: Loss of T790 M mutation at resistance was correlated with early progression and overall survival in response to osimertinib treatment in Chinese patients with NSCLC harboring acquired T790 M mutation.