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Antibody-based regimens targeting PD-1/PD-L1 and VEGF/VEGFR in advanced or metastatic NSCLC: a meta-analysis of RCTs
Wenjie Mao1, Zeqi Tang2, Yu Chen3
1Department of Pulmonary and Critical Care Medicine, Ningbo Hospital of Integrated Traditional Chinese and Western Medicine, Ningbo, Zhejiang, China.
Background:
Antibody-based regimens targeting programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) include conventional PD-1/PD-L1 inhibitors combined with anti-angiogenic monoclonal antibodies and PD-1/VEGF or PD-L1/VEGF bispecific antibodies, with or without chemotherapy. However, the clinical efficacy of these regimens in advanced or metastatic non-small cell lung cancer (NSCLC) remains unclear. This meta-analysis systematically evaluated their efficacy.
Materials And Methods:
PubMed, EMBASE, Web of Science, ClinicalTrials.gov, and the Cochrane Library were searched to identify relevant randomized controlled trials (RCTs) published up to February 2026. The main outcomes analyzed were progression-free survival (PFS) and overall survival (OS), with the hazard ratio (HR) and 95% confidence interval (95%CI) used for statistical analysis. The study protocol was registered on PROSPERO (CRD420251126421).
Results:
Eleven RCTs were included in the analysis, with 4,426 participants. Antibody-based regimens targeting PD-1/PD-L1 and VEGF/VEGFR, with or without chemotherapy, were associated with better PFS (HR = 0.65, 95%CI: 0.57-0.75, p<0.001) and OS (HR = 0.79, 95%CI: 0.71-0.87, p<0.001) compared with the control regimen. For PFS, favorable subgroup estimates were observed in men (HR = 0.61), squamous histology (HR = 0.57), patients with liver metastases (HR = 0.49), those with higher PD-L1 expression (tumor proportion score (TPS)≥50%: HR = 0.65), those with epidermal growth factor receptor (EGFR) mutation (HR = 0.60). For OS, favorable subgroup estimates were observed in patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS)=1 (HR = 0.80), men (HR = 0.80), smokers (HR = 0.82), those with liver metastases (HR = 0.57), those with PD-L1 TPS 1%-49% (HR = 0.67), and EGFR-mutant patients (HR = 0.80).
Conclusion:
Antibody-based regimens targeting PD-1/PD-L1 and VEGF/VEGFR improve prognosis in advanced or metastatic NSCLC, with potential variation in benefit across clinicopathological characteristics.
Insights
Antibody-based regimens targeting programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) significantly improve progression-free survival and overall survival in advanced non-small cell lung cancer. Benefits vary across patient subgroups, indicating personalized treatment potential.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Advanced or metastatic non-small cell lung cancer (NSCLC) presents significant treatment challenges.
- Current antibody-based regimens target programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) pathways.
- The clinical efficacy of these combined or bispecific antibody strategies in NSCLC requires systematic evaluation.
Purpose of the Study:
- To systematically evaluate the efficacy of antibody-based regimens targeting PD-1/PD-L1 and VEGF/VEGFR in advanced or metastatic NSCLC.
- To compare the outcomes of these novel regimens against control treatments.
- To identify patient subgroups who may benefit most from these therapeutic strategies.
Main Methods:
- A systematic meta-analysis of randomized controlled trials (RCTs) was conducted.
- Searches were performed across major databases including PubMed, EMBASE, Web of Science, ClinicalTrials.gov, and the Cochrane Library up to February 2026.
- Progression-free survival (PFS) and overall survival (OS) were the primary endpoints, analyzed using hazard ratios (HR) and 95% confidence intervals (95%CI).
Main Results:
- Eleven RCTs involving 4,426 participants were analyzed.
- Antibody-based regimens demonstrated significant improvements in both PFS (HR=0.65) and OS (HR=0.79) compared to control regimens.
- Favorable PFS outcomes were noted in specific subgroups, including men, squamous histology, liver metastases, high PD-L1 expression (TPS≥50%), and EGFR mutations.
- OS benefits were observed in patients with ECOG PS=1, men, smokers, liver metastases, moderate PD-L1 expression (TPS 1%-49%), and EGFR mutations.
Conclusions:
- Antibody-based regimens targeting PD-1/PD-L1 and VEGF/VEGFR pathways represent a promising therapeutic approach for advanced or metastatic NSCLC.
- These regimens significantly improve patient prognosis, enhancing both PFS and OS.
- The observed variations in benefit across different clinicopathological characteristics suggest potential for personalized treatment strategies in NSCLC management.
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