Antibody-based regimens targeting PD-1/PD-L1 and VEGF/VEGFR in advanced or metastatic NSCLC: a meta-analysis of RCTs

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.