Clinical outcomes of targeted treatment strategies for primary non-small cell lung cancer with MET alterations: a systematic review and meta-analysis
- 1Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease
- 2Graduate School, Guangzhou Medical University
- 3The First Clinical Medical College, Guangzhou Medical University
Abstract
Background: Primary non-small cell lung cancer (NSCLC) with mesenchymal-epithelial transition factor ( MET ) gene alterations, including exon 14 skipping mutations and amplification, represents a distinct molecular subtype with unique therapeutic challenges. While multiple tyrosine kinase inhibitor (TKI) strategies have been developed, their comparative efficacy and safety remain systematically unquantified, particularly across different MET alteration types.
Methods: We conducted a single-arm meta-analysis of clinical trials evaluating MET-targeted therapies in patients with primary MET -altered NSCLC. A systematic search of PubMed, Embase, Cochrane Library, and major conference proceedings was performed up to August 31, 2025. The primary outcome was progression-free survival (PFS), with secondary outcomes including overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Data were synthesized using R software (version 4.4.2). The protocol was registered with PROSPERO (CRD420251265925).
Findings: A total of 25 studies involving 1,636 participants were included. MET -TKIs demonstrated the highest pooled ORR of 49% (95% CI 46-52%) and DCR of 84% (95% CI 81-87%), significantly outperforming ALK / ROS-1 -TKIs (ORR 38%, DCR 66%) and other strategies. Subgroup analysis revealed that patients with MET amplification had consistently lower response rates compared to those with exon 14 skipping mutations across all TKI treatments (ORR 22% vs. higher in exon 14). Regarding safety, MET -TKIs were associated with a high incidence of any-grade AEs (90%), particularly peripheral edema. Notably, the combination of MET -TKI and programmed cell death protein 1 (PD-1) inhibitors carried the highest risk of severe (Grade ≥3) AEs (49%), primarily due to overlapping toxicities such as pneumonitis.
Interpretation: Selective MET-targeted therapies show robust clinical efficacy and represent a viable therapeutic strategy for NSCLC patients with MET exon 14 skipping mutations. However, current TKI strategies show limited efficacy for MET -amplified tumors, highlighting an unmet need for optimized approaches in this subgroup. While effective, MET -TKIs require careful management of adverse events, and their combination with immune checkpoint inhibitors warrants caution due to significant toxicity risks. Future research should focus on standardizing MET amplification definitions and exploring novel combination therapies to overcome resistance.
Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251265925 , identifier CRD420251265925.
Related
- Technical overview and clinical outcomes of transabdominal strategies to eliminate or neutralize staple-line intersection during low anterior resection: a systematic review.
- Fungal Periprosthetic Joint Infection: A Systematic Review and Meta-analysis of Treatment Approaches and Clinical Outcomes.
- HEPATIC ENCEPHALOPATHY IN ALCOHOL-RELATED CIRRHOSIS:A SYSTEMATIC REVIEW OF CLINICAL CHARACTERISTICS, THERAPEUTIC STRATEGIES, AND PROGNOSTIC OUTCOMES Revisão Sistemática da Incidência, Estratégias Terapêuticas e Determinantes de Desfecho
- Photobiomodulation Treatment Parameters and Clinical Outcomes Following Periodontal Soft-Tissue Surgery: A Systematic Review
- Clinical outcomes of graftless implant rehabilitation strategies for the posterior atrophic maxilla: A systematic review and meta-analysis
BibTeX
@article{meng2026clinical,
title = {{Clinical outcomes of targeted treatment strategies for primary non-small cell lung cancer with MET alterations: a systematic review and meta-analysis}},
author = {Zixi Meng and Hongsheng Deng and Jingwen Han and Wei Ruan and Yaoxing Xiao and Hongtai Huang and Jingqi Wang and Jun Huang},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.1824182},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1824182/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical outcomes of targeted treatment strategies for primary non-small cell lung cancer with MET alterations: a systematic review and meta-analysis
AU - Zixi Meng
AU - Hongsheng Deng
AU - Jingwen Han
AU - Wei Ruan
AU - Yaoxing Xiao
AU - Hongtai Huang
AU - Jingqi Wang
AU - Jun Huang
PY - 2026
DA - 2026/11/04
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1824182
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1824182/full
AB - Background: Primary non-small cell lung cancer (NSCLC) with mesenchymal-epithelial transition factor ( MET ) gene alterations, including exon 14 skipping mutations and amplification, represents a distinct molecular subtype with unique therapeutic challenges. While multiple tyrosine kinase inhibitor (TKI) strategies have been developed, their comparative efficacy and safety remain systematically unquantified, particularly across different MET alteration types. Methods: We conducted a single-arm meta-analysis of clinical trials evaluating MET-targeted therapies in patients with primary MET -altered NSCLC. A systematic search of PubMed, Embase, Cochrane Library, and major conference proceedings was performed up to August 31, 2025. The primary outcome was progression-free survival (PFS), with secondary outcomes including overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Data were synthesized using R software (version 4.4.2). The protocol was registered with PROSPERO (CRD420251265925). Findings: A total of 25 studies involving 1,636 participants were included. MET -TKIs demonstrated the highest pooled ORR of 49% (95% CI 46-52%) and DCR of 84% (95% CI 81-87%), significantly outperforming ALK / ROS-1 -TKIs (ORR 38%, DCR 66%) and other strategies. Subgroup analysis revealed that patients with MET amplification had consistently lower response rates compared to those with exon 14 skipping mutations across all TKI treatments (ORR 22% vs. higher in exon 14). Regarding safety, MET -TKIs were associated with a high incidence of any-grade AEs (90%), particularly peripheral edema. Notably, the combination of MET -TKI and programmed cell death protein 1 (PD-1) inhibitors carried the highest risk of severe (Grade ≥3) AEs (49%), primarily due to overlapping toxicities such as pneumonitis. Interpretation: Selective MET-targeted therapies show robust clinical efficacy and represent a viable therapeutic strategy for NSCLC patients with MET exon 14 skipping mutations. However, current TKI strategies show limited efficacy for MET -amplified tumors, highlighting an unmet need for optimized approaches in this subgroup. While effective, MET -TKIs require careful management of adverse events, and their combination with immune checkpoint inhibitors warrants caution due to significant toxicity risks. Future research should focus on standardizing MET amplification definitions and exploring novel combination therapies to overcome resistance. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251265925 , identifier CRD420251265925.
SN - 2234-943X
ER -