Efficacy and Safety of Programmed Death 1/Programmed Death-Ligand 1 Plus Cytotoxic T-Lymphocyte-Associated Antigen 4
Wei Ren1, Yingying Fang2, Yujing He3
1General Family Medicine, Ningbo Yinzhou No. 2 Hospital, Ningbo, Zhejiang, China.
Background:
This meta-analysis aims to investigate the efficacy and safety of programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) combined with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors for patients with advanced or metastatic non-small cell lung cancer (NSCLC).
Methods:
Authors conducted a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Medline for randomized controlled trials comparing the prognosis and safety of PD-1/PD-L1 plus CTLA-4 inhibitors with other therapies for advanced or metastatic NSCLC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effect sizes. The primary outcomes of this study were overall survival (OS) and progression-free survival.
Results:
A total of 4943 patients diagnosed with stage III/IV advanced or metastatic NSCLC were included in the analysis of the 6 randomized controlled trials. The results showed that patients receiving dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors had a longer survival time compared with the control group (HR = 0.88, P = 0.044). However, no statistically significant difference was observed in progression-free survival (HR = 0.95, P = 0.579). Subgroup analysis revealed better OS in the interventional group for patients aged >65 years (HR = 0.88, P = 0.076), smokers (HR = 0.81, P = 0.036), and those with a tumor mutational burden (TMB) ≥20 mut/Mb (HR = 0.66, P < 0.001). Conversely, the control group demonstrated superior OS in patients with TMB <20 mut/Mb (HR = 1.14, P = 0.048). In addition, the statistical results indicated a lower incidence rate of any-grade anemia in the dual immunotherapy group compared with the control group (RR = 0.32, P = 0.04).
Conclusions:
This meta-analysis demonstrates the effectiveness and safety of dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors for treating advanced or metastatic NSCLC. Its efficacy is influenced by certain clinical and pathological factors, such as age, smoking status, and TMB.
Insights
Dual immunotherapy combining programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors improves overall survival in advanced non-small cell lung cancer (NSCLC). This approach also shows a reduced risk of anemia.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Advanced or metastatic non-small cell lung cancer (NSCLC) presents significant treatment challenges.
- Programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors are emerging immunotherapies.
- Combination strategies are being explored to enhance treatment efficacy.
Purpose of the Study:
- To evaluate the efficacy and safety of combined PD-1/PD-L1 and CTLA-4 inhibitors in advanced or metastatic NSCLC.
- To compare dual immunotherapy outcomes against other treatments through meta-analysis.
Main Methods:
- A systematic literature search was performed across major databases (PubMed, Embase, Cochrane Library, Web of Science, Scopus, Medline).
- Included randomized controlled trials (RCTs) comparing dual immunotherapy with control groups for advanced/metastatic NSCLC.
- Overall survival (OS) and progression-free survival (PFS) were primary endpoints, analyzed using Hazard Ratios (HRs) and 95% Confidence Intervals (CIs).
Main Results:
- Analysis of 6 RCTs involving 4943 patients showed dual immunotherapy significantly improved OS (HR = 0.88, P = 0.044).
- No significant difference in PFS was observed (HR = 0.95, P = 0.579).
- Subgroup analyses indicated improved OS for patients >65 years, smokers, and those with tumor mutational burden (TMB) ≥20 mut/Mb. Patients with TMB <20 mut/Mb had better OS with the control group. Anemia incidence was lower with dual immunotherapy (RR = 0.32, P = 0.04).
Conclusions:
- Dual immunotherapy with PD-1/PD-L1 and CTLA-4 inhibitors is effective and safe for advanced/metastatic NSCLC.
- Treatment efficacy is modulated by patient factors including age, smoking status, and tumor mutational burden (TMB).
- This combination therapy offers a promising treatment option, with specific patient subgroups benefiting more significantly.
