Synthesis and Tyrosine Kinase Inhibitory Activity of a Series of 2-Amino-8H-pyrido[2,3-d]pyrimidines:  Identification of Potent, Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitors

1998 ◽  
Vol 41 (22) ◽  
pp. 4365-4377 ◽  
Author(s):  
Diane H. Boschelli ◽  
Zhipei Wu ◽  
Sylvester R. Klutchko ◽  
H. D. Hollis Showalter ◽  
James M. Hamby ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Receptor Tyrosine Kinase ◽  
Inhibitory Activity ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Kinase Inhibitory Activity ◽  
Receptor Tyrosine Kinase Inhibitors

scholarly journals Efficacy of Next-Generation EGFR-TKIs in Patients With Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 19 ◽  
pp. 153303382094042
Author(s):  
Yi-Tian Qi ◽  
Yi Hou ◽  
Liang-Chen Qi
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Receptor Tyrosine Kinase Inhibitors

Background: The efficacy of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer who have failed first-generation epidermal growth factor receptor-tyrosine kinase inhibitors still remains under investigation. Objective: The aim of this meta-analysis was to systematically assess the efficacy and safety profiles of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer who failed first-generation epidermal growth factor receptor-tyrosine kinase inhibitors. Methods: We performed a comprehensive search of several electronic databases up to September 2018 to identify clinical trials. The primary end point was overall survival, progression-free survival, disease controlled rate, objective response rate, and adverse events. Epidermal growth factor receptor-tyrosine kinase inhibitor emergent severe adverse events (grade ≥ 3) were analyzed. Odds ratio along with 95% confidence interval were utilized for main outcome analysis. Results: In total, we had 3 randomized controlled trials in this analysis. The group of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors had significantly improved progression-free survival (odds ratio = 0.34, 95% confidence interval = 0.29-0.40, P < .00001), as well as objective response rate (odds ratio = 10.48, 95% confidence interval = 3.87-28.34, P < .00001) and disease controlled rate (odds ratio = 6.03, 95% confidence interval = 4.41-8.25, P < .00001). However, there was no significant difference in overall survival with next-generation epidermal growth factor receptor-tyrosine kinase inhibitors (odds ratio = 1.05, 95% confidence interval = 0.85-1.31, P = .66). Meanwhile, the odds ratio for treatment-emergent severe adverse events (diarrhea, rash/acne, nausea, vomiting, anemia) between patients who received next-generation epidermal growth factor receptor-tyrosine kinase inhibitors and those who received first-generation epidermal growth factor receptor-tyrosine kinase inhibitors did not show safety benefit ( P > .05). Conclusions: Next-generation epidermal growth factor receptor-tyrosine kinase inhibitors were shown to be the better agent to achieve higher response rate and longer progression-free survival in patients with non-small cell lung cancer as the later-line therapy for previously treated patients with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors. Meanwhile, they did not achieve benefit in overall survival and safety compared with the chemotherapy group. Further research is needed to develop a database of all EGFR mutations and their individual impacts on the various treatments.

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