Efficacy and Safety of PD-1/PD-L1 plus CTLA-4 antibodies +/- Other Therapies in Lung Cancer: A Systematic Review and Meta-Analysis

Background: Immune checkpoint inhibitors have brought hope for patients with advanced lung cancer, among which PD-1/PD-L1 and CTLA-4 inhibitors have achieved considerable results. This meta-analysis aims to investigate the efficacy and safety of PD-1/PD-L1 combined with CTLA-4 antibodies in patients with advanced lung cancer. Materials and Methods: Randomized controlled trials (RCTs) study of PD-1/PD-L1 combined with CTLA-4 inhibitors for advanced lung cancer was searched in the database for systematic review and meta-analysis. Results: The meta-analysis finally included 4 trials (actually 3 trials), and the results showed that the overall response rate of PD-1/PD-L1 combined with CTLA-4 inhibitor was higher than that of the control group (ORR = 2.29 [95% CI 1.58 3.32], P <0.0001). PFS significantly improved compared with conventional treatment (HR = 0.69 [95% CI 0.56, 0.85], P = 0.0005), which was statistically significant. OS also improved but did not statistically significant (HR = 0.80 [95% CI 0.61, 1.05], P = 0.11). PD-1/PD-L1 combined with CTLA-4 inhibitors had a higher incidence of adverse reactions than conventional treatment (OR = 1.72 [95% CI 0.59, 5.09], P = 0.33), but the incidence of grade≥3 AEs was lower than the control group (OR = 0.96 [95% CI 0.64, 1.44], P = 0.85). Conclusion: Double checkpoint inhibitor PD-1/PD-L1 combined with CTLA-4 antibody has synergistic anti-cancer activity and improved ORR and PFS in lung cancer. Adverse reactions are more common than conventional treatment, but are generally controllable. Therefore, PD-1/PD-L1 combined with CTLA-4 inhibitors provides a beacon for the treatment of advanced lung cancer, which has guiding significance for the treatment selection in the future.