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 journalArticle

80 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

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Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Mutation
Therapeutics
Adenocarcinoma of lung
Taiwan
Disease-Free Survival
Exons
Survival

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

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

In: Journal of Thoracic Oncology, Vol. 10, No. 5, 30.05.2015, p. 793-799.

Research output: Contribution to journalArticle

Chiu, CH, 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 2015, 'Epidermal growth factor receptor tyrosine Kinase inhibitor treatment response in advanced lung adenocarcinomas with G719X/L861Q/S768I mutations', Journal of Thoracic Oncology, vol. 10, no. 5, pp. 793-799. https://doi.org/10.1097/JTO.0000000000000504
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. / Epidermal growth factor receptor tyrosine Kinase inhibitor treatment response in advanced lung adenocarcinomas with G719X/L861Q/S768I mutations. In: Journal of Thoracic Oncology. 2015 ; Vol. 10, No. 5. pp. 793-799.
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T1 - Epidermal growth factor receptor tyrosine Kinase inhibitor treatment response in advanced lung adenocarcinomas with G719X/L861Q/S768I mutations

AU - Chiu, Chao Hua

AU - Yang, Cheng Ta

AU - Shih, Jin Yuan

AU - Huang, Ming Shyan

AU - Su, Wu Chou

AU - Lai, Ruay Sheng

AU - Wang, Chin Chou

AU - Hsiao, Shih Hsin

AU - Lin, Yu Ching

AU - Ho, Ching Liang

AU - Hsia, Te Chun

AU - Wu, Ming Fang

AU - Lai, Chun Liang

AU - Lee, Kang Yun

AU - Lin, Chih Bin

AU - Yu-Wung Yeh, Diana

AU - Chuang, Chi Yuan

AU - Chang, Fu Kang

AU - Tsai, Chun Ming

AU - Perng, Reury Perng

AU - Chih-Hsin Yang, James

PY - 2015/5/30

Y1 - 2015/5/30

N2 - 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.

AB - 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.

KW - Adenocarcinoma

KW - EGFR mutations

KW - Epidermal growth factor receptor

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KW - Tyrosine kinase inhibitor

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