SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1673115
This article is part of the Research TopicEGFR-Targeted Therapy in Lung Cancer: Unraveling Molecular Regulation, Overcoming Resistance, and Advancing Precision Clinical PracticeView all articles
Efficacy and Safety Analysis of Treatment in Patients with EGFR-mutated Advanced NSCLC Who Progressed on TKIs: A Systematic Review and Meta-Analysis
Provisionally accepted
- 1Department of Thoracic Oncology, Clinical Research Big data Center,Jilin Cancer Hospital, Changchun, China
- 2Biobank,Jilin Cancer Hospital, Changchun, China
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Background: The treatment of patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) whose disease progresses after tyrosine-kinase inhibitors (TKIs) treatment has become a research hotspot. Objective: To identify effective and safe treatment options for patients with EGFR-mutated advanced NSCLC who progressed on TKIs. Methods: We searched databases including PubMed, Cochrane Library, and major international conference abstracts (2018–2023) to identify phase II/III randomized controlled trials (RCTs) and single-arm studies of EGFR-mutated advanced NSCLC post-TKI progression from April 2018 to June 2024. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade ≥3 adverse events (AEs), treatment-related AEs (TRAEs), and TRAE-related deaths. Bayesian network meta-analysis and individual patient data (IPD) meta-analysis were performed to compare treatment efficacy and safety. Results: This meta-analysis included randomized controlled trials (RCTs) and 5 single-arm phase 2 trials (3116 patients) evaluating 7 treatment regimens for EGFR-mutated advanced NSCLC post-TKI progression. In the network meta-analysis (NMA), amivantamab plus lazertinib plus chemotherapy (amiva-lazer-chemo) yielded the highest PFS (surface under the cumulative ranking curve [SUCRA]: 0.88; hazard ratio [HR] vs chemotherapy, 0.44; 95% CI, 0.32-0.61), followed by AK112 plus chemotherapy (SUCRA: 0.79; HR, 0.46; 95% CI, 0.32-0.67). All regimens significantly improved PFS compared with chemotherapy alone. Amivantamab plus chemotherapy ranked highest for ORR (SUCRA: 0.82; odds ratios [OR] vs chemotherapy, 3.16; 95% CI, 1.09-9.41). No significant OS differences were observed. Amiva-lazer-chemo had the highest grade ≥3 AE incidence. IPD analysis confirmed superior PFS for amiva-lazer-chemo (median, 8.45 months; 95% CI, 7.02-9.26; HR vs chemotherapy, 0.47; 95% CI, 0.40-0.55; P < .001). Moderate ORR heterogeneity (I² = 52.2%) and high AE heterogeneity (I² = 79.5%-92.1%) were noted. Conclusion: In this meta-analysis of patients with TKI-resistant EGFR-mutated advanced NSCLC, the amiva-lazer-chemo regimen was associated with longer PFS at both the study level and individual patient level. Combination therapy with anti-angiogenic agents also represents a viable treatment strategy for this patient population.
Keywords: EGFR-mutated NSCLC, Immunotherapy, Network meta-analysis, efficacy, Safety
Received: 25 Jul 2025; Accepted: 15 Oct 2025.
Copyright: © 2025 Zhang, Li, Cui and Li. 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: Hui Li, 181966963@qq.com
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