SynthesisFrontiers in oncology2026
Efficacy of PD-1/PD-L1 inhibitors combined with multi-targeted anti-angiogenic TKIs in advanced or metastatic NSCLC: A meta-analysis based on RCTs.
Synthesis in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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7 authors.
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Abstract
Background: The efficacy of combining programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors with multi-targeted anti-angiogenic tyrosine kinase inhibitors (TKIs) in advanced or metastatic non-small cell lung cancer (NSCLC) remains controversial. This study therefore aimed to systematically evaluate the efficacy of this combination regimen in patients with advanced or metastatic NSCLC. Methods: We systematically searched PubMed, EMBASE, Web of Science, ClinicalTrials.gov, and the Cochrane Library databases for relevant randomized controlled trials (RCTs) up to July 2025. The primary outcomes were progression-free survival (PFS) and overall survival (OS), analyzed using the hazard ratio (HR) and 95% confidence interval (95%CI). Results: A total of six RCTs were included, involving 2,787 participants. Results demonstrated that the intervention group receiving PD-1/PD-L1 inhibitors combined with anti-angiogenic TKIs showed improved PFS compared with the control group (HR = 0.82, 95%CI: 0.69-0.97, p=0.021). However, no statistically significant difference was observed between the two groups in OS (HR = 0.97, 95%CI: 0.88-1.07, p=0.554). Subgroup analyses indicated that the PFS benefit was more pronounced in patients aged<65 years (HR = 0.78, 95%CI: 0.64-0.94), female (HR = 0.73, 95%CI: 0.57-0.92), never-smokers (HR = 0.72, 95%CI: 0.53-0.98), white people (HR = 0.85, 95%CI: 0.72-0.99), with non-squamous NSCLC (HR = 0.82, 95%CI: 0.66-1.01, p=0.064), high PD-L1 expression (tumor proportion score (TPS)≥50%) (HR = 0.78, 95%CI: 0.63-0.96), Eastern Cooperative Oncology Group (ECOG) performance status (PS)=1 (HR = 0.78, 95%CI: 0.64-0.96), no liver (HR = 0.78, 95%CI: 0.64-0.96) or brain (HR = 0.73, 95%CI: 0.53-1.00, p=0.054) metastases, and those receiving first-line therapy (HR = 0.72, 95%CI: 0.54-0.97). No significant difference in OS was observed in all subgroups (all p>0.05). Conclusion: The combination of PD-1/PD-L1 inhibitors and anti-angiogenic TKIs significantly improved PFS in patients with advanced or metastatic NSCLC but did not translate into an OS benefit. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251126527.
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