Combined Anti-PD-1/PD-L1 and Anti-angiogenic Therapy: An Emerging Direction for Future NSCLC Treatment

Lung cancer remains the leading cause of cancer-related mortality. The 5-year survival rate for advanced non-small cell lung cancer (NSCLC) is only 20%-30%, highlighting an urgent need for more effective therapeutic strategies. Immune checkpoint inhibitors and anti-angiogenic agents are now widely used in clinical practice and have significantly prolonged patient survival. However, their efficacy and safety remain constrained by multiple reasons. This review systematically outlines the synergistic mechanisms and recent advances of combined anti-PD-1/PD-L1 and anti-angiogenic therapy. It also evaluates the clinical value of novel bispecific antibodies in NSCLC, with a specific focus on their potential advantages in patients with comorbidities. By systematically synthesizing preclinical and clinical data from 2020 to 2026, this article analyzes the mechanistic roles of the combination strategy. The clinical efficacy and safety profile are comprehensively assessed. Current evidence demonstrates that combining anti-PD-1/PD-L1 agents with anti-angiogenic therapy synergistically remodels the tumor immune microenvironment. This approach enhances T cell infiltration and function and effectively overcomes monotherapy resistance. Clinical studies have confirmed that this regimen extends median overall survival (mOS) by 4.8 months. Bispecific antibodies developed on this foundation optimize pharmacokinetic matching and improve safety profiles. These single-agent therapies show promising clinical potential for managing NSCLC with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). In conclusion, combined therapy has become a pivotal direction in NSCLC systemic treatment. Future research should prioritize optimizing treatment regimens, refining real-world safety assessments, and expanding clinical application in patients with complex comorbidities to address current unmet therapeutic needs.