Epidermal growth factor receptor tyrosine Kinase inhibitor treatment response in advanced lung adenocarcinomas with G719X/L861Q/S768I mutations

Chao Hua Chiu, Cheng Ta Yang, Jin Yuan Shih, Ming Shyan Huang, Wu Chou Su, Ruay Sheng Lai, Chin Chou Wang, Shih Hsin Hsiao, Yu Ching Lin, Ching Liang Ho, Te Chun Hsia, Ming Fang Wu, Chun Liang Lai, Kang Yun Lee, Chih Bin Lin, Diana Yu-Wung Yeh, Chi Yuan Chuang, Fu Kang Chang, Chun Ming Tsai, Reury Perng PerngJames Chih-Hsin Yang

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

Abstract

Background: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for advanced lung adenocarcinomas with common EGFR mutations. Preclinical studies have suggested that uncommon G719X, L861Q, and S768I mutations are also sensitive to EGFR-TKIs. However, the efficacy of EGFR-TKIs in patients with these uncommon mutations remains unclear. Methods: A nationwide survey was performed to collect data from gefitinib and erlotinib treatment outcomes of patients with stage IIIB/IV lung adenocarcinoma bearing EGFR G719X/L861Q/S768I mutations. The results were compared with those regarding patients with exon 19 deletions or L858R mutations. Results: One hundred and sixty-one patients with uncommon EGFR mutations were enrolled from 18 institutes throughout Taiwan. Mutations of G719X, L861Q, S768I, G719X + L861Q, and G719X + S768I were observed in 78, 57, 7, 9, and 10 patients, respectively. After receiving EGFR-TKI treatment, patients with uncommon mutations exhibited a significantly inferior tumor response rate (41.6% vs. 66.5%; p <0.001) and progression-free survival (median, 7.7 vs. 11.4 months; p <0.001) than patients with common mutations. Among the patients who used EGFR-TKIs as first-line treatment, there was a significant difference in overall survival between these two groups of patients (median, 24.0 vs. 29.7 months; p = 0.005). Conclusion: Gefitinib and erlotinib are active in patients with G719X/L861Q/S768I mutations; however, less effective than in those with common mutations.

Original languageEnglish
Pages (from-to)793-799
Number of pages7
JournalJournal of Thoracic Oncology
Volume10
Issue number5
DOIs
Publication statusPublished - May 30 2015

Keywords

  • Adenocarcinoma
  • EGFR mutations
  • Epidermal growth factor receptor
  • Lung cancer
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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