Authors
Yike Zhang, Haozhe Wang, Xinyue Yang, Changhai Lei
Published in
Frontiers in immunology. Volume 16. Pages 1605877. Epub Sep 10, 2025.
Abstract
Despite advances in targeted therapies and immune checkpoint inhibitors (ICIs), the prognosis for advanced non-small cell lung cancer (NSCLC) remains poor. Bispecific antibodies (BsAbs) represent an emerging class of dual-target immunotherapies, yet their comparative efficacy and safety profiles lack comprehensive quantitative synthesis.
This systematic review and meta-analysis (PROSPERO CRD420251005168) adhered to PRISMA guidelines. We systematically searched PubMed, Web of Science, Scopus, and Embase through March 2025 for phase III randomized controlled trials (RCTs) comparing dual-target immunotherapies with conventional therapies in advanced NSCLC. Primary outcomes were progression-free survival (PFS) and overall survival (OS); secondary outcomes included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). Risk of bias was assessed using Cochrane RoB 2.0. Random-effects models were used for data synthesis.
Six RCTs (n=3,063 patients) were included. Dual-target immunotherapies significantly improved PFS (HR= 0.58, 95% CI: 0.43-0.78; p<0.001) and ORR (RR=1.29,95%CI: 1.01-1.64; p=0.04) compared to conventional therapies. No significant OS (HR=0.84,95% CI: 0.68-1.05; p=0.13) or DCR (RR=1.09, 95% CI: 0.92-1.30; p=0.30) benefits were observed. Subgroup analyses stratified by mechanism showed no statistically significant differences in efficacy and safety between dual-target immunotherapies with different targets of action. Safety analyses revealed increased risks of any adverse events (RR=1.05; 95%CI: 1.02-1.09), grade≥3 AEs (RR=1.63; 95% CI: 1.37-1.94), serious AEs (RR=1.49; 95%CI:1.31-1.69) and AEs leading to treatment discontinuation (RR=2.49; 95% CI: 1.72-3.62) with dual-target immunotherapies.
Our findings, based on phase III RCTs, are limited by substantial heterogeneity among included studies. Dual-target immunotherapies demonstrate superior PFS and ORR in NSCLC but are associated with increased toxicity, particularly with EGFR/MET-targeted agents. While offering a promising therapeutic advance, safety optimization and biomarker-driven patient selection are critical for clinical translation. Further trials are needed to validate long-term survival benefits and refine risk-benefit profiles.
https://www.crd.york.ac.uk/prospero/, identifier CRD420251005168.
PMID:
41000392
Bibliographic data and abstract were imported from PubMed on 26 Sep 2025.
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