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Efficacy of Next-Generation EGFR-TKIs in Patients With Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized
Yi-Tian Qi1, Yi Hou2, Liang-Chen Qi3
1Department of Radiology, China-Japan Union Hospital, Jilin University, Changchun, China.
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.
Insights
Next-generation EGFR-TKIs improve progression-free survival and response rates in advanced non-small cell lung cancer after first-generation treatment. However, they do not offer overall survival or safety benefits compared to chemotherapy.
Area of Science:
- Oncology
- Pharmacology
Background:
- Advanced non-small cell lung cancer (NSCLC) treatment efficacy after first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is under investigation.
- Next-generation EGFR-TKIs represent a potential therapeutic option for patients who have progressed on earlier treatments.
Purpose of the Study:
- To systematically evaluate the efficacy and safety of next-generation EGFR-TKIs in advanced NSCLC patients with prior first-generation EGFR-TKI failure.
- To compare outcomes including overall survival, progression-free survival, and adverse events.
Main Methods:
- A meta-analysis of randomized controlled trials identified through comprehensive database searches up to September 2018.
- Primary endpoints included overall survival, progression-free survival, disease control rate, objective response rate, and adverse events.
- Analysis of EGFR-TKI emergent severe adverse events (grade ≥ 3) using odds ratios and 95% confidence intervals.
Main Results:
- Next-generation EGFR-TKIs significantly improved progression-free survival (P < .00001), objective response rate (P < .00001), and disease controlled rate (P < .00001).
- No significant difference in overall survival was observed between next-generation EGFR-TKIs and controls (P = .66).
- Safety analysis revealed no significant benefit for next-generation EGFR-TKIs regarding treatment-emergent severe adverse events (P > .05).
Conclusions:
- Next-generation EGFR-TKIs demonstrate superior efficacy in improving response rates and progression-free survival for previously treated advanced NSCLC patients.
- These agents did not show benefits in overall survival or safety compared to chemotherapy.
- Further research is warranted to correlate specific EGFR mutations with treatment outcomes.
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