Different characteristics and survival in non‐small cell lung cancer patients with primary and acquired EGFR T790M mutation

• Published in: International journal of cancer 2019-06, Vol.144 (11), p.2880-2886
• Main Authors: Wang, Shuyuan, Yan, Bo, Zhang, Yanwei, Xu, Jianlin, Qiao, Rong, Dong, Yu, Zhang, Bo, Zhao, Yiming, Zhang, Lele, Qian, Jie, Lu, Jun, Zhao, Ruiying, Han, Baohui
• Format: Article
• Language: English
• Subjects: Acrylamides - therapeutic use; Adult; Aged; Aged, 80 and over; Aniline Compounds - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Cell survival; Disease Progression; EGFR T790M mutation; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - genetics; Exons - genetics; Female; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; Medical research; Middle Aged; Mutation; Non-small cell lung carcinoma; NSCLC; Osimertinib; Patient Selection; Patients; primary and acquired; Progression-Free Survival; Protein Kinase Inhibitors - therapeutic use; Response Evaluation Criteria in Solid Tumors; Survival; Survival Analysis; Targeted cancer therapy; TKI
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32015

Primary epidermal growth factor receptor (EGFR) T790M mutation can be occasionally identified in previous untreated nonsmall cell lung cancer (NSCLC) patients. To compare clinical characteristics and outcomes in patients with primary and acquired EGFR T790M mutation, we collected the data of patients diagnosed with EGFR mutation from 2012 to 2017 in Shanghai Chest Hospital. Primary EGFR T790M mutation was identified in 61 patients (1.1%; 95% confidence interval (CI): 0.8%–1.3%) of 5685 TKI‐naive EGFR mutant patients. Acquired T790M mutation was detected in 98 patients (50.3%; 95%CI: 43.2%–57.3%) of 195 TKI‐treated patients. T790M mutation always coexisted with sensitizing EGFR mutations. Primary EGFR T790M always coexisted with 21L858R (46/61) whereas acquired T790M coexisted with 19del (68/98), (p < 0.001). Among them, 18 patients with primary T790M mutation received osimertinib and 72 patients with acquired T790M mutation received osimertinib. The median progression‐free survival (PFS) of osimertinib was significantly longer in primary T790M group (17.0 months, 95%CI:14.0–20.0 months) compared to acquired T790M group (10.0 months, 95%CI:8.6–11.4 months, p = 0.022). However, the median overall survival (OS) of acquired T790M mutation patients was significantly longer compared to that of primary T790M mutation patients who received osimertinib (50.4 months vs. 29.9 months, p = 0.016). Our findings suggest that primary T790M mutation likely coexists with 21L858R while acquired mutation likely coexists with 19del. Both mutations showed good response to osimertinib. Patients with primary T790M mutation experienced greater benefits from osimertinib. However, patients with acquired T790M mutation had a better overall survival during the entire clinical treatment. What's New? EGFR tyrosine kinase inhibitors (TKIs) are first‐line treatment in non‐small cell lung cancer (NSCLC). While acquired resistance mechanisms to EGFR‐TKIs include emergence of the EGFR mutation T790M, primary EGFR T790M mutation was also detected in untreated patients. Differences in molecular and clinical characteristics between the two subsets of patients and treatment efficacy however remain unclear. This study found that primary T790M mutation always coexists with EGFR 21L858R, and acquired T790M mutation with 19del alternations. Both subsets showed good response to osimertinib, with greater benefits for patients with primary T790M mutation. However, patients with acquired T790M mutation