Meta-analysis shows dual ICI therapy improves survival in advanced metastatic non-small cell lung cancer

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). 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). 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, age 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.