Prediction for response duration to epidermal growth factor receptor-tyrosine kinase inhibitors in EGFR mutated never smoker lung adenocarcinoma

Hye Ryun Kim, Byoung Chul Cho, Hyo Sup Shim, Sun Min Lim, Se Kyu Kim, Joon Chang, Dae Joon Kim, Joo Hang Kim

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Objectives: Among non-small cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations, ~20-30% exhibit de novo resistance to EGFR-tyrosine kinase inhibitor (TKI). The aim of this study was to examine whether mutations in the EGFR-downstream genes may be associated with de novo resistance to EGFR-TKIs in EGFR mutation-positive patients. Materials and methods: Sixty-eight never-smoker adenocarcinoma patients with an activating EGFR mutation were included in the mutational analysis and 55 patients treated with EGFR-TKIs were analyzed for the treatment outcomes to EGFR-TKIs. We concurrently analyzed mutations in PIK3CA, PTEN, AKT and STK11, which are all EGFR-downstream genes. Mutations in PIK3CA, PTEN, AKT, and STK11 were analyzed by polymerase chain reaction-based sequencing. Results: PIK3CA mutations were detected in 4.4% (3/68) of patients, PTEN mutations in 16.1% (11/68), AKT mutations in 5.9% (4/68), and STK11 mutations in 13.2% (9/68). One patient with an activating exon 21 L858R mutation concomitantly had an exon 20 T790M mutation in EGFR. The proportion of patients who had mutations in EGFR-downstream genes was 32.4% (22/68). When we analyzed the treatment outcome of 55 patients treated with EGFR-TKI, the presence of mutations in EGFR-downstream genes correlated with a poor overall response rate to EGFR-TKIs (63.6 vs.14.5% in patients with mutation in EGFR-downstream gene, P< 0.0001), shorter median progression-free survival (12.0 vs. 3.0 months, P= 0.060), and shorter median overall survival (18.9 vs. 25.0 months, P= 0.048). Conclusion: Mutations in the EGFR-downstream genes may confer resistance to EGFR-TKIs and result in poor treatment outcomes in never-smoker adenocarcinoma patients with activating EGFR mutations.

Original languageEnglish
Pages (from-to)374-382
Number of pages9
JournalLung Cancer
Volume83
Issue number3
DOIs
Publication statusPublished - 2014 Mar

Bibliographical note

Funding Information:
This work was supported by a grant of the Health Fellowship Foundation and a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea ( HI13C1948 ).

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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