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.
Targeting 14-3-3ζ Overcomes Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Lung Adenocarcinoma via BMP2/Smad/ID1 Signaling
