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

Int J Cancer. 2019 Jun 1;144(11):2880-2886. doi: 10.1002/ijc.32015. Epub 2019 Jan 3.

Abstract

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.

Keywords: EGFR T790M mutation; NSCLC; Osimertinib; TKI; primary and acquired.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Disease Progression
  • ErbB Receptors / genetics
  • Exons / genetics
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality*
  • Male
  • Middle Aged
  • Mutation
  • Patient Selection
  • Progression-Free Survival
  • Protein Kinase Inhibitors / therapeutic use*
  • Response Evaluation Criteria in Solid Tumors
  • Survival Analysis

Substances

  • Acrylamides
  • Aniline Compounds
  • Protein Kinase Inhibitors
  • osimertinib
  • EGFR protein, human
  • ErbB Receptors