Yingying Fang

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 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.

Background This study aims to investigate the effect of PD-1/PD-L1 immunotherapy on cardiac-related adverse events in patients with advanced or metastatic lung cancer. Methods We conducted a detailed search in PubMed, Web of Science, Cochran, and Embase for articles on the application of immunotherapy for lung cancer and report cardiac-related adverse events with respect to myocardial ischemia, pericardial effusion, myocarditis, and electrophysiology. The dichotomous variables were assessed by relative risk (RR) and 95% confidence intervals (CI). Results A total of 7132 subjects were included in 12 phase III randomized controlled trials (RCTs). The results showed that under the fixed effects model, the probability of cardiac-related adverse events in pericardial effusion was higher in the experimental group than in the control group (RR 2.30, 95% CI 1.01–5.21, P = 0.05). Under the random effects model, there was no statistical difference between the two groups (RR 2.03, 95% CI 0.81–5.12, P = 0.13). No statistical difference is observed between the experimental group and the control group (under the fixed effects model and the random effects model) for other cardiac-related adverse events, including myocarditis, acute coronary syndrome, myocardial infarction, acute myocardial infarction, myocardial ischemia, unstable angina, ventricular tachycardia, supraventricular tachycardia, tachycardia, bradycardia, atrial flutter, atrial fibrillation, cardiac failure, cardiac arrest, cardiopulmonary failure, acute heart failure, cardiac arrest (all P > 0.05). Conclusions PD-1/PD-L1 immunotherapy in advanced or metastatic lung cancer is generally safe for cardiac-related adverse events.