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Optimized selection of three major EGFR-TKIs in advanced EGFR-positive non-small cell lung cancer: a network
Yaxiong Zhang1,2,3, Jin Sheng1,2,3, Yunpeng Yang1,2,3
1Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Background:
To answer which epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the best choice for advanced non-small cell lung cancer (NSCLC) EGFR mutants.
Results:
16 phase III randomized trials involving 2962 advanced NSCLC EGFR mutants were enrolled. Multiple treatment comparisons showed different EGFR-TKIs shared equivalent curative effect in terms of all outcome measures among the overall, chemo-naïve and previously treated patients. Rank probabilities showed that erlotinib and afatinib had potentially better efficacy compared with gefitinib in both of the overall and chemo-naïve patients. Potentially survival benefit of erlotinib was also observed in previously treated patients compared with gefitinib. Additionally, EGFR-TKI showed numerically greater survival benefit in 19 Del compared with chemotherapy, while it was opposite in 21 L858R. Furthermore, afatinib, erlotinib and gefitinib had high, moderate and low risk of rash & diarrhea, respectively, while the occurrence of elevated liver transaminase was more common in gefitinib.
Methods:
Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events were extracted from included studies. Efficacy and toxicity of all included treatments were integrated by network meta-analyses.
Conclusion:
Our study indicated a high efficacy-high toxicity pattern of afatinib, a high efficacy-moderate toxicity pattern of erlotinib and a medium efficacy-moderate toxicity pattern of gefitinib. Recommended EGFR-TKI should be suggested according to patients' tolerability and therapeutic efficacy in clinical practice. Moreover, the treatment for advanced EGFR-positive NSCLC might be different between 19 Del and 21 L858R.
Insights
Erlotinib and afatinib show potential efficacy advantages over gefitinib for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. Treatment choice depends on patient tolerability and specific EGFR mutations (19 Del vs. 21 L858R).
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Advanced non-small cell lung cancer (NSCLC) with EGFR mutations presents a therapeutic challenge.
- Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a key treatment modality.
- Optimal selection among various EGFR-TKIs remains an area of active investigation.
Purpose of the Study:
- To compare the efficacy and toxicity of different EGFR-TKIs in advanced NSCLC patients with EGFR mutations.
- To identify the most effective EGFR-TKI based on available clinical trial data.
- To inform clinical decision-making for personalized NSCLC treatment.
Main Methods:
- Network meta-analysis of 16 phase III randomized controlled trials.
- Inclusion of 2962 patients with advanced NSCLC and EGFR mutations.
- Extraction and integration of data on objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events.
Main Results:
- Multiple EGFR-TKIs demonstrated comparable curative effects across various patient subgroups.
- Erlotinib and afatinib showed potentially superior efficacy compared to gefitinib in overall and chemotherapy-naïve patients.
- Afatinib, erlotinib, and gefitinib exhibited high, moderate, and low risks of rash and diarrhea, respectively; gefitinib was associated with more elevated liver transaminases.
- EGFR-TKI offered a survival benefit in 19 Del mutations, while chemotherapy was favored in 21 L858R mutations.
Conclusions:
- Afatinib, erlotinib, and gefitinib exhibit distinct efficacy-toxicity profiles: high efficacy-high toxicity (afatinib), high efficacy-moderate toxicity (erlotinib), and medium efficacy-moderate toxicity (gefitinib).
- Clinical recommendations for EGFR-TKIs should consider individual patient tolerability and therapeutic efficacy.
- Treatment strategies for advanced EGFR-positive NSCLC may need to be tailored based on specific mutations, such as 19 Del versus 21 L858R.
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