Efficacy of PD-1/PD-L1 plus CTLA-4 inhibitors in advanced/metastatic NSCLC: a meta-analysis based on RCTs

Background: Dual immune checkpoint inhibitor (ICI) therapy (PD-1/PD-L1+CTLA-4 inhibitors) has emerged as a promising strategy, but its efficacy and optimal patient selection remain uncertain. This meta-analysis aimed to evaluate the efficacy of dual ICI therapy in advanced/metastatic non-small cell lung cancer (NSCLC) based on randomized controlled trials (RCTs). Methods: We systematically searched Cochrane Library, Embase, Web of Science, and PubMed from inception to August 2025 for RCTs comparing dual ICI therapy (PD-1/PD-L1+CTLA-4 inhibitors) versus control treatments in advanced/metastatic NSCLC. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Results: Ten RCTs comprising 6, 369 patients were included. The OS (HR = 0. 84, 95%CI 0. 76-0. 92, p=0. 003) and PFS (HR = 0. 78, 95%CI 0. 68-0. 89, p=0. 002) of patients who received dual ICI treatment were significantly better than those in the control group. Subgroup analyses of the OS revealed significant benefits, including: squamous, non-squamous, PD-1 inhibitor, PD-L1 inhibitor, bone metastases, without bone metastases, male, age0. 05 and Pᵢnteraction <0. 05). Conclusion: Dual ICI therapy with PD-1/PD-L1 plus CTLA-4 inhibitors improves prognosis in advanced/metastatic NSCLC, with efficacy difference across subgroups. TMB may serve as a complementary predictive biomarker for dual immunotherapy. Systematic review registration: PROSPERO, identifier: CRD420251147483.