Related Experiment Video
Updated: May 28, 2026
Semi-automatic PD-L1 Characterization and Enumeration of Circulating Tumor Cells from Non-small Cell Lung Cancer Patients by Immunofluorescence
Published on: August 14, 2019
Efficacy of PD-1/PD-L1 plus CTLA-4 inhibitors in advanced/metastatic NSCLC: a meta-analysis based on RCTs
Tianfu Dai1, Yu Chen2, Xuelian Dai1
1The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China.
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, age<65, ECOG = 0, Asian, PD-L1 TPS<1%, PD-L1 TPS≥50%, with high TMB (TMB≥10 or TMB≥20), smokers, brain metastases, without liver metastases, and when the control group received chemotherapy, placebo, first-line (1L) or non 1L (all p<0.05). Conversely, no significant benefit was observed in patients aged≥65, low TMB (TMB<10 or TMB<20), non-smokers, without brain metastases, or when the control group received monotherapy immunotherapy (all p>0.05 and P_interaction <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.
Insights
Dual immune checkpoint inhibitor (ICI) therapy significantly improves survival outcomes for advanced non-small cell lung cancer (NSCLC). Efficacy varies by patient subgroup, suggesting TMB as a potential biomarker.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Dual immune checkpoint inhibitor (ICI) therapy, combining PD-1/PD-L1 and CTLA-4 inhibitors, shows promise for advanced/metastatic non-small cell lung cancer (NSCLC).
- Optimal patient selection and definitive efficacy data for dual ICI therapy in NSCLC are still under investigation.
Purpose of the Study:
- To evaluate the efficacy of dual ICI therapy compared to control treatments in patients with advanced/metastatic NSCLC.
- To identify patient subgroups that benefit most from dual ICI therapy.
Main Methods:
- Systematic literature search of randomized controlled trials (RCTs) in major databases (PubMed, Embase, etc.) up to August 2025.
- Meta-analysis of 10 RCTs involving 6,369 patients, focusing on overall survival (OS) and progression-free survival (PFS).
Main Results:
- Dual ICI therapy significantly improved both OS (HR=0.84) and PFS (HR=0.78) compared to control groups.
- Significant benefits were observed across various subgroups, including different cancer types, PD-1/PD-L1 inhibitor use, presence of metastases, patient demographics, and PD-L1 expression levels.
- Tumor mutational burden (TMB) emerged as a potential predictive biomarker, with high TMB associated with greater efficacy.
Conclusions:
- Dual ICI therapy offers a significant survival advantage for patients with advanced/metastatic NSCLC.
- Patient selection is crucial, as efficacy differs across subgroups, highlighting the role of TMB as a complementary predictive biomarker.
