What question did this study set out to answer?

The aim is to evaluate the efficacy of combining PD-1/PD-L1 inhibitors with anti-angiogenic TKIs in advanced or metastatic NSCLC.

April 5, 2026Open Access

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

Key Points

The aim is to evaluate the efficacy of combining PD-1/PD-L1 inhibitors with anti-angiogenic TKIs in advanced or metastatic NSCLC.
Systematic search of databases including PubMed and Cochrane Library for RCTs.
Primary outcomes measured were progression-free survival and overall survival using hazard ratios.
Six RCTs with 2,787 participants were included for analysis.
Intervention group showed improved progression-free survival (HR = 0.82, p=0.021) compared to control.
No significant difference in overall survival (HR = 0.97, p=0.554).
Subgroup analyses indicated stronger PFS benefits in specific demographics, including patients aged <65 years and women.

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 aged65 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 p0.05). 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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Cite This Study

Tang et al. (Wed,) studied this question.

synapsesocial.com/papers/69d1fb20a79560c99a0a1908 https://doi.org/https://doi.org/10.3389/fonc.2026.1799126

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