Efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitor versus chemotherapy for advanced lung cancer

Abstract

Background: This meta-analysis was performed to compare efficacy and tolerability between antiprogrammed cell death (PD-1)/programmed cell death-ligand-1 (PD-L1) + anticytotoxic T-lymphocyte-associated protein-4 (CTLA-4) treatment and chemotherapy in advanced lung cancer. Methods: Cochrane Library, Embase, and PubMed databases were searched for potential articles. The fixed-effect model or random-effect model was adopted for pooled analysis based on the I 2 and P -value. Results: Six articles with 1338 patients were identified and subjected to meta-analysis. Compared with chemotherapy, anti-PD-1/PD-L1 + anti-CTLA-4 treatment could significantly improve the overall survival (hazard ratio [HR] = 0.78, 95%confidence interval [CI]: 0.71–0.84, P = .21) and progression-free survival (HR = 0.77, 95%CI: 0.71–0.83, P = .30) of advanced lung cancer patients. Moreover, there was no obvious difference in the incidence of 3 to 4 adverse events (AEs) serious adverse reactions (HR = 1.35, 95%CI: 0.66–2.74, P < .00001) between the 2 treatment groups, but the incidence rates of AEs leading to discontinuation (HR = 2.56, 95%CI: 1.53–4.30, P < .00001) and AEs leading to death (HR = 2.10, 95%CI: 1.21–3.63, P = .20) were higher. Furthermore, no remarkable differences in objective response rate (HR = 1.31, 95%CI: 0.97–1.77, P = .02) were observed between the 2 groups. Conclusion: Our meta-analysis revealed that PD-1/PD-L1 inhibitors plus CTLA-4 inhibitor could markedly improve the endpoint outcomes of patients compared with chemotherapy alone, and did not significantly increase the serious adverse reactions. Thus, it can serve as a new treatment strategy for advanced lung cancer.

[Retracted] Clinical Efficacy and Safety Analysis of PD‐1/PD‐L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non‐Small‐Cell Lung Cancer: A Systematic Review and Meta‐Analysis

“…Meta-analysis results showed that pembrolizumab combined with chemotherapy improved 1-year survival rate and prolonged OS, with statistically significant differences compared with chemotherapy alone, while complete response rate, PFS, and chemotherapy alone showed no statistically significant differences. Relevant studies [ 36 – 38 ] also showed that pembrolizumab combined with chemotherapy had a higher proportion of grade 3 and 4 leukopenia, rash, and infusion reaction than chemotherapy alone, and the difference was statistically significant, but there was no increase in the mortality rate. Therefore, pembrolizumab is effective and safe.…”

Therapeutic strategies for gastric cancer targeting immune cells: Future directions

“…In addition, therapeutic strategies targeting immune cells have also achieved good results in combination with other treatments, such as combination with chemotherapy drugs. It has been confirmed that drug therapy plays a role in remodeling the tumor immune microenvironment, such as decreased density of CD8 + cells and increased density of FoxP3 + cells and B cells (CD20 + ) in PTs after NAC, but PD-L1 expression did not change ( 338 ). In addition, PD-L1 expression and CD8 + T-cell infiltration were increased in the tumor microenvironment after treatment with the targeted drug anti-VEGFR2 antibody RAM in GC, and PD-1 expression in eT regs cells and CD8 + T cells was significantly reduced in TILs ( 136 ).…”

Lung Cancer Immunotherapy: Beyond Common Immune Checkpoints Inhibitors

“…An improved OS with the combination therapy in the ITT population was shown. However, according to the analysis, no statistically significant difference between the two groups was found for patients with PD-L1 < 1%, thus narrowing the benefit from this combination for PD-L1 ≥ 1% expression [ 68 ].…”

“…TIGIT is a protein composed of an extracellular Ig variable domain, a transmembrane domain and a short intracellular domain endowed with one immunoreceptor tyrosine-based inhibitory motif (ITIM) and one immunoglobulin tyrosine tail (ITT)-like motif [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , …”

“…TIGIT belongs to the family of Poliovirus Receptor (PVR)-like proteins and shares sequence homology with other members of the PVR-like family [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , ...…”