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

• Published in: Journal of thoracic oncology 2015-05, Vol.10 (5), p.793-799
• Main Authors: Chiu, Chao-Hua, Yang, Cheng-Ta, Shih, Jin-Yuan, Huang, Ming-Shyan, Su, Wu-Chou, Lai, Ruay-Sheng, Wang, Chin-Chou, Hsiao, Shih-Hsin, Lin, Yu-Ching, Ho, Ching-Liang, Hsia, Te-Chun, Wu, Ming-Fang, Lai, Chun-Liang, Lee, Kang-Yun, Lin, Chih-Bin, Yu-Wung Yeh, Diana, Chuang, Chi-Yuan, Chang, Fu-Kang, Tsai, Chun-Ming, Perng, Reury-Perng, Chih-Hsin Yang, James
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adult; Aged; Aged, 80 and over; Disease-Free Survival; EGFR mutations; Epidermal growth factor receptor; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; Erlotinib Hydrochloride - therapeutic use; Female; Gefitinib; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Middle Aged; Mutation; Protein Kinase Inhibitors - therapeutic use; Quinazolines - therapeutic use; Survival Rate; Treatment Outcome; Tyrosine kinase inhibitor
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1097/JTO.0000000000000504

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