• 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, Yu-Wung Yeh Diana D Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan., Chi-Yuan Chuang, Fu-Kang Chang, Chun-Ming Tsai, Reury-Perng Perng, and Chih-Hsin Yang James J Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan..
• Department of Chest Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan. Electronic address: jhchiou@vghtpe.gov.tw.
• J Thorac Oncol. 2015 May 1; 10 (5): 793-799.

BackgroundEpidermal 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.MethodsA 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.ResultsOne 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).ConclusionGefitinib and erlotinib are active in patients with G719X/L861Q/S768I mutations; however, less effective than in those with common mutations.

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