Efficacy of PD-1/PD-L1 and LAG-3 immune checkpoint inhibitors in the treatment of patients with solid tumor.

Abstract / Summary

Lymphocyte activation gene 3 (LAG-3) inhibitor, demonstrates limited antitumor efficacy when used alone. Therefore, the clinical efficacy of combining LAG-3 with other immune checkpoint inhibitors warrants further investigation. The objective of this study is to investigate the efficacy of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and LAG-3 inhibitors in the treatment of patients with solid tumor. We systematically and independently conducted a literature search using PubMed, Cochrane, and Web of Science, up to December 2025. We selected original studies investigating the efficacy of PD-1/PD-L1 combined with LAG-3 inhibitors in the treatment of solid tumors. Two authors independently extracted trial characteristics and intervention details using a predefined form. Objective response rate (ORR), disease control rate (DCR), median overall survival (OS) or progression-free survival (PFS) with their corresponding 95% confidence intervals (CIs) were used to evaluate the primary outcomes. A total of six randomized controlled trials were included in the analysis. The results indicated that PD-1/PD-L1 combined with LAG-3 inhibitors significantly improved the DCR (0.66, P < 0.001) and ORR (0.25, P < 0.001) in patients with solid tumors. The median PFS of combination therapy was 3.51 months (P < 0.001). Subgroup analyses revealed that the Chinese population (ORR 0.4, P = 0.001) and individuals aged < 60 years (0.08, P < 0.001) derived greater benefit from PD-1/PD-L1 combined with LAG-3 inhibitor therapy. Additionally, PD-1/PD-L1 combined with LAG-3 inhibitors significantly improved the ORR in patients with nasopharyngeal carcinoma (0.24, P = 0.003). PD-1/PD-L1 combined with LAG-3 inhibitors demonstrates higher response rates, but the survival outcomes remain unclear. Further, patients with NPC, Chinese population, and individuals aged < 60 years may potentially benefit from the combination therapy.

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