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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment Response in Advanced Lung Adenocarcinomas with G719X/L861Q/S768I Mutations

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J Thorac Oncol. 2015 May;10(5):793-9. doi: 10.1097/JTO.0000000000000504. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment Response in Advanced Lung Adenocarcinomas with G719X/L861Q/S768I Mutations.

Chiu CH1, Yang CT, Shih JY, Huang MS, Su WC, Lai RS, Wang CC, Hsiao SH, Lin YC, Ho CL, Hsia TC, Wu MF, Lai CL, Lee KY, Lin CB, Yu-Wung Yeh D, Chuang CY, Chang FK, Tsai CM, Perng RP, Chih-Hsin Yang J.

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1*Department of Chest Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan; †Department of Thoracic Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; ‡Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan §Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan; ‖Department of Internal Medicine, National Cheng Kung University Hospital and National Cheng Kung University, Tainan, Taiwan; ¶Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; #Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan;

**Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; ††Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi and Chang Gung University, Taoyuan, Taiwan;

‡‡department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan; §§Department of Respiratory Therapy, China Medical University Hospital and China Medical University, Taichung, Taiwan; ‖‖School of Medicine, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan; ¶¶Department of Internal Medicine, Buddhist Dalin Tzu Chi Hospital, Chiayi and Tzu Chi University, Hualien, Taiwan; ##Department of Pulmonary Medicine, Shuang Ho Hospital and Taipei Medical University, Taipei, Taiwan; ***Department of Internal Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan;

†††Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; and; ‡‡‡Department of Internal Medicine, Ren-ai Branch, and

§§§Department of Internal Medicine, Zhong-xiao Branch, Taipei City Hospital, Taipei, Taiwan.

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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.

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