Response to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma with the Rare Epidermal Growth Factor Receptor Mutation S768I: a Retrospective Analysis and Literature Review

2016 ◽  
Vol 12 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Xiaoli Zhu ◽  
Qianming Bai ◽  
Yongming Lu ◽  
Peng Qi ◽  
Jianhui Ding ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Literature Review ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Retrospective Analysis ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Epidermal Growth

scholarly journals De Novo T790M Mutation in an L858R Epidermal Growth Factor Receptor Mutant-Associated Lung Adenocarcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3074
Author(s):  
Takumi Fujiwara ◽  
Tetsu Kobayashi ◽  
Taro Yasuma ◽  
Corina N. D’Alessandro-Gabazza ◽  
Masaaki Toda ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Growth Factor Receptor ◽  
T790m Mutation ◽  
Epidermal Growth

Background: Lung cancer is the leading cause of mortality for cancer worldwide. A point mutation in exon 21 of the epidermal growth factor receptor resulting in the substitution of arginine for leucine at position 858 (L858R) is a frequent cause of lung adenocarcinoma. Tyrosine kinase inhibitors are effective for treating patients with lung cancer associated with mutant epidermal growth factor receptors but most tumors become resistant shortly after treatment. The substitution of methionine for threonine at position 790 (T790M) on exon 20 is the most frequently acquired mutation leading to resistance to tyrosine kinase inhibitors. Whether the T790M mutation occurred after tyrosine kinase inhibitor therapy or it already existed before therapy is unclear. Methods: Here, we developed mice with tetracycline-inducible lung-specific expression of the full-length genomic DNA of the human epidermal growth factor receptor containing an L858R mutation or both L858R and T790M mutations and evaluated de novo T790M mutation in untreated transgenic mice carrying a single L858R EGFR mutation. Results: The L858R mutation-associated lung adenocarcinoma acquired de novo T790 mutation without previous therapy. Conclusions: The results of this study suggest that lung tumors may spontaneously acquire T790M mutations without any drug-related selective pressure.

scholarly journals Comparison of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung adenocarcinoma harboring different epidermal growth factor receptor mutation types

2020 ◽  
Author(s):  
Sojung Park ◽  
Sung Yong Lee ◽  
Dojin Kim ◽  
Yun Su Sim ◽  
Jeong-Seon Ryu ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Egfr Tkis

Abstract Background: Epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation types are associated with efficacy of EGFR TKIs. We investigated the clinical outcomes of afatinib, erlotinib, and gefitinib according to EGFR mutation type in patients with lung adenocarcinoma.Methods: Between May 2010 and December 2018, we investigated 363 patients with advanced lung adenocarcinoma harboring EGFR mutations who received EGFR TKIs. Efficacies of EGFR TKIs such as response rate, progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated according to exon 19 deletion (E19del), L858R point mutation (L858R) and uncommon mutations. Results: The frequency of E19del was 48.2%, that of L858R was 42.4%, and that of uncommon mutations was 9.4%. E19del and L858R were associated with superior PFS and OS compared with uncommon mutations. Erlotinib showed significantly inferior OS than other TKIs (30.8 ± 3.3 in erlotinib vs. 39.1 ± 4.3 in afatinib vs. 48.4 ± 6.3 in gefitinib; p = 0.031) in patients with L858R. Gefitinib showed significantly inferior PFS (4.6 ± 1.1 in gefitinib vs. 11.6 ± 2.7 in afatinib vs. 10.6 ± 2.7 in erlotinib; p = 0.049) in patients with uncommon mutations. Conclusion: Afatinib was significantly associated with a longer PFS, presenting constant effectiveness in all EGFR mutation types. Caution may be needed on the use of erlotinib for L858R and the use of gefitinib for uncommon EGFR mutations.

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