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Efficacy of PD-1/PD-L1 inhibitors combined with multi-targeted anti-angiogenic TKIs in advanced or metastatic NSCLC:

Zeqi Tang1, Xiaoming Zhang2, Zhanqi Sun3

  • 1The Fifth School of Clinical Medical, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

Frontiers in Oncology
|April 17, 2026
PubMed
Abstract

Insights

Combining programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors with anti-angiogenic tyrosine kinase inhibitors (TKIs) improved progression-free survival in advanced non-small cell lung cancer (NSCLC). However, this combination did not significantly impact overall survival in patients with NSCLC.

Area of Science:

  • Oncology
  • Immunotherapy
  • Pharmacology

Background:

  • The combination of programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and multi-targeted anti-angiogenic tyrosine kinase inhibitors (TKIs) for advanced or metastatic non-small cell lung cancer (NSCLC) has shown controversial efficacy.
  • This systematic review aims to consolidate evidence on the efficacy of this combination regimen in advanced or metastatic NSCLC patients.

Purpose of the Study:

  • To systematically evaluate the efficacy of combining PD-1/PD-L1 inhibitors with anti-angiogenic TKIs in patients with advanced or metastatic NSCLC.
  • To analyze primary outcomes including progression-free survival (PFS) and overall survival (OS).

Main Methods:

  • A systematic literature search was conducted across major databases (PubMed, EMBASE, Web of Science, ClinicalTrials.gov, Cochrane Library) for relevant randomized controlled trials (RCTs) up to July 2025.
  • Six RCTs involving 2,787 participants were included. Primary outcomes (PFS and OS) were analyzed using hazard ratios (HR) and 95% confidence intervals (95%CI).

Main Results:

  • The combination therapy demonstrated a significant improvement in PFS (HR=0.82, 95%CI: 0.69-0.97, p=0.021) compared to control groups.
  • No statistically significant difference was observed in overall survival (OS) between the combination group and control group (HR=0.97, 95%CI: 0.88-1.07, p=0.554).
  • Subgroup analyses revealed that PFS benefits were more pronounced in specific patient populations, including those aged <65 years, females, never-smokers, white individuals, patients with non-squamous NSCLC, high PD-L1 expression (TPS≥50%), ECOG PS=1, no liver or brain metastases, and those receiving first-line therapy.

Conclusions:

  • The combination of PD-1/PD-L1 inhibitors and anti-angiogenic TKIs significantly improves PFS in advanced or metastatic NSCLC patients.
  • This improved PFS did not translate into a significant overall survival benefit in the studied patient population.
Keywords:
NSCLCPD-1/PD-L1 inhibitorsPFSmeta-analysismulti-targeted anti-angiogenic TKIsos

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