Efficacy and safety of EGFR-TKI for EGFR-mutated NSCLC: systematic review and network meta-analysis.

Background: Afatinib, Dacomitinib, Osimertinib, Aumolertinib, Furmonertinib, Gefitinib, Erlotinib, and Icotinib have all been shown to work and be safe for people with epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) in recent years, but differences in efficacy, safety, and lack of comparative trials cause clinical confusion in treatment selection. This study analyzes their efficacy and safety via network meta-analysis to inform clinical decisions.

Method: We searched PubMed, Embase, Cochrane Library, and Web of Science for pertinent studies. The objective response rate (ORR), median progression-free survival (mPFS), time to treatment failure (TTF), median overall survival (mOS), and adverse events (AEs) were then extracted.

Result: In the efficacy analysis, Afatinib had the greatest ORR at SUCRA=95.9%, outperforming Gefitinib (SUCRA=22.7%) and Icotinib (SUCRA=30.7%). Furmonertinib had the longest mPFS of SUCRA=92.6%, outperforming Gefitinib (SUCRA=10.1%) and Afatinib (SUCRA=11.8%). Dacomitinib had the best TTF (SUCRA=84.1%), followed by Afatinib and Icotinib, which had a longer TTF than Gefitinib (SUCRA=7.0%). In safety evaluations, Aumolertinib performed best in overall grade 1-5 AEs (SUCRA=30.0%) and high-grade (≥3) AEs safety (SUCRA=9.5%), while Afatinib had the worst overall safety rating (SUCRA=68.3%), and Osimertinib had the worst high-grade (≥3) AEs profile. Afatinib and Osimertinib showed significantly greater grade ≥3 AEs compared to Furmonertinib, Icotinib, and Gefitinib. Aumolertinib had reduced frequencies of rash and diarrhea, while Afatinib/Dacomitinib had increased risks of vomiting.

Conclusion: This network meta-analysis reveals that in first-line treatment, the third-generation EGFR-TKI Furmonertinib has exceptional advantages in mPFS and safety and is suited for patients with long-term disease control needs. Although second-generation Afatinib has the highest objective remission rate, it also increases the possibility of grade ≥3 AEs. Clinically, personalized programs should be devised based on the patient's mutation type, tolerance, and other factors. More head-to-head trials will be required in the future to validate the findings and optimize treatment techniques.