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

Sha Zhao, Xuefei Li, Chao Zhao, Tao Jiang, Yijun Jia, Jinpeng Shi, Yayi He, Jiayu Li, Fei Zhou, Guanghui Gao, Wei Li, Xiaoxia Chen, Chunxia Su, Shengxiang Ren, Caicun Zhou
Lung Cancer: Journal of the International Association for the Study of Lung Cancer 2019, 128: 33-39

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.


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