Zan Haifeng, Xu Min, Guo Ping, Yu Xinlin
Department of Respiratory, Affiliated Hospital Chengdu University Chengdu 610000, Sichuan, China.
Department of Cardiology, Affiliated Hospital Chengdu University Chengdu 610000, Sichuan, China.
Int J Clin Exp Pathol. 2025 Jul 15;18(7):386-404. doi: 10.62347/DWIW6941. eCollection 2025.
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.
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.
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.
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.
近年来，阿法替尼、达可替尼、奥希替尼、阿美替尼、伏美替尼、吉非替尼、厄洛替尼和埃克替尼已被证明对表皮生长因子受体（EGFR）阳性的非小细胞肺癌（NSCLC）患者有效且安全，但疗效差异、安全性问题以及缺乏对比试验导致治疗选择上的临床困惑。本研究通过网状Meta分析来分析它们的疗效和安全性，为临床决策提供依据。
我们在PubMed、Embase、Cochrane图书馆和Web of Science中检索相关研究。然后提取客观缓解率（ORR）、中位无进展生存期（mPFS）、治疗失败时间（TTF）、中位总生存期（mOS）和不良事件（AE）。
在疗效分析中，阿法替尼的ORR最高，SUCRA=95.9%，优于吉非替尼（SUCRA=22.7%）和埃克替尼（SUCRA=30.7%）。伏美替尼的mPFS最长，SUCRA=92.6%，优于吉非替尼（SUCRA=10.1%）和阿法替尼（SUCRA=11.8%）。达可替尼的TTF最佳（SUCRA=84.1%），其次是阿法替尼和埃克替尼，它们的TTF比吉非替尼更长（SUCRA=7.0%）。在安全性评估中，阿美替尼在总体1-5级AE（SUCRA=30.0%）和高级别（≥3级）AE安全性（SUCRA=9.5%）方面表现最佳，而阿法替尼的总体安全性评级最差（SUCRA=68.3%），奥希替尼的高级别（≥3级）AE情况最差。与伏美替尼、埃克替尼和吉非替尼相比，阿法替尼和奥希替尼的≥3级AE明显更多。阿美替尼的皮疹和腹泻发生率降低，而阿法替尼/达可替尼的呕吐风险增加。
这项网状Meta分析表明，在一线治疗中，第三代EGFR-TKI伏美替尼在mPFS和安全性方面具有突出优势，适合有长期疾病控制需求的患者。虽然第二代阿法替尼的客观缓解率最高，但也增加了≥3级AE的可能性。临床上，应根据患者的突变类型、耐受性等因素制定个性化方案。未来需要更多的头对头试验来验证研究结果并优化治疗技术。
