SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1586332
This article is part of the Research TopicProgress in Molecular Mechanisms and Targeted Therapies for Solid Tumor MicroenvironmentsView all 8 articles
Comparative Analysis of First-Generation Epidermal Growth Factor Receptor Inhibitors Combined with Chemotherapy Versus Third-Generation Epidermal Growth Factor Receptor Inhibitors in the Treatment of Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Provisionally accepted
- Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
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In advanced non-small cell lung cancer (NSCLC) with EGFR mutations, thirdgeneration EGFR TKIs (3 rd -G TKIs) are currently the preferred first-line treatment.Previous studies have demonstrated that combining first-generation EGFR TKIs with chemotherapy (1 st -G TKIs + chemo) also significantly enhances efficacy compared to 1 st -G TKIs alone. This study aims to compare the effectiveness of 1 st -G TKIs + chemo against 3 rd -G TKIs.We conducted an indirect meta-analysis of randomized controlled trials comparing 1 st -G TKIs + chemo to 3 rd -G TKIs. Randomized controlled trials (RCTs) were searched from the PubMed, Embase and Cochrane Library databases. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). Data were analyzed using inverse variance and Mantel-Haenszel methods.Ten RCTs with 3,014 patients met the inclusion criteria. Direct comparisons indicated that 1 st -G TKIs + chemo significantly improved PFS (HR 0.54, P<0.001), OS (HR 0.62, P<0.001), and ORR (RR 1.21, P<0.001) compared to 1 st -G TKIs alone. Indirect comparisons between 1 st -G TKIs + chemo and 3 rd -G TKIs revealed no significant differences in PFS (HR 1.17; 95% CI, 0.98 to 1.40; P=0.075) or OS (HR 0.78; 95% CI,
Keywords: EGFR mutant, chemotherapy, targeted therapy, Advanced non small cell lung cancer, combined therapy
Received: 12 Mar 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Peng, Yu, Zhu, Liang, Qiu, HONG and Yixin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
SHAODONG HONG, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
Zhou Yixin, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
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