Brain metastasis, EGFR mutation subtype and generation of EGFR-TKI jointly influence the treatment outcome of patient with EGFR-mutant NSCLC

Jia Shiuan Ju, Allen Chung Cheng Huang, Pi Hung Tung, Chi Hsien Huang, Tzu Hsuan Chiu, Chin Chou Wang, How Wen Ko, Fu Tsai Chung, Ping Chih Hsu, Yueh Fu Fang, Yi Ke Guo, Chih Hsi Scott Kuo*, Cheng-Ta Yang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review


Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation is brain metastasis (BM)-prone. We determined the impact of this hallmark, along with EGFR subtype and generation of tyrosine kinase inhibitor (TKI) treatment, on patients’ outcome. 553 metastatic EGFR-mutant NSCLC patients received front-line EGFR-TKI treatment. Progression-free survival (PFS), overall survival (OS) and secondary T790M rate were analysed. BM was observed in 211 (38.2%) patients. BM (HR 1.20 [95% CI 0.99–1.48]; p = 0.053), ECOG PS 0–1 (HR 0.71 [95% CI 0.54–0.93]; p = 0.014) and afatinib treatment (HR 0.81 [95% CI 0.66–0.99]; p = 0.045) were associated with PFS. Afatinib-treated patients without BM demonstrated a significantly longer PFS (16.3 months) compared to afatinib-treated patients with BM (13.7 months) and to gefitinib/erlotinib-treated patients with (11.1 months) or without BM (14.2 months; p < 0.001). CNS-only progression trended higher in afatinib-treated patients. ECOG PS 0–1 (HR 0.41 [95% CI 0.31–0.56]; p < 0.001) and EGFR L858R mutation (HR 1.46 [95% CI 1.13–1.88]; p = 0.003), but not BM, were the predictors for OS. BM (OR 2.02 [95% CI 1.02–4.08]; p = 0.040), afatinib treatment (OR 0.26 [95% CI 0.12–0.50]; p < 0.001) and EGFR L858R mutation (OR 0.55 [95% CI 0.28–1.05]; p = 0.070) were associated with secondary T790M rate. In BM patients, gefitinib/erlotinib-treated ones with 19 deletion mutation and afatinib-treated ones with L858R mutation had the highest and the lowest T790M rate (94.4% vs. 27.3%, p < 0.001), respectively. BM and generation of EGFR-TKI jointly impact PFS and secondary T790M rate in patients with EGFR-mutant NSCLC, whereas OS was mainly associated with EGFR subtype.

Original languageEnglish
Article number20323
Pages (from-to)20323
JournalScientific Reports
Issue number1
StatePublished - 21 11 2023

Bibliographical note

© 2023. The Author(s).


  • Humans
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Afatinib/therapeutic use
  • Erlotinib Hydrochloride/therapeutic use
  • Gefitinib/therapeutic use
  • ErbB Receptors/genetics
  • Lung Neoplasms/drug therapy
  • Protein Kinase Inhibitors/therapeutic use
  • Mutation
  • Treatment Outcome
  • Brain Neoplasms/drug therapy


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