The Correlation Between the Influencing Factors and Efficacy of Immune Checkpoint Inhibitor Therapy: an Umbrella Meta-Analysis of Randomized Controlled Trials

Objective We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy. Materials and methods We systematically searched three databases (PubMed, Web of Science and Embase) up to 20 February 2023. Extracting the effect size and 95% confidence intervals for overall survival (OS), progression-free survival (PFS) and the objective response rate (ORR). Results A total of 65 articles were included. We identified the following factors that benefit ICI therapy: smoking status (PFS: 0.72 [0.62, 0.84], p < .001), chemotherapy (PFS: 0.68 [0.58, 0.79], p < .001), expression of programmed cell death ligand 1(PD-L1) (>= 1%, >= 5%, or >= 10%) (>= 1%: 0.76 [0.71,0.82], p < .001; >= 5%: 0.62 [0.52, 0.74], p < .001; >= 10%: 0.42 [0.30, 0.59], p < .001). We also identified three adverse factors: epidermal growth factor receptor mutations (OS: 1.57 [1.06, 2.32], p = .02), with liver metastases (OS: 1.16 [1.02,1.32], p = .02) and antibiotics (OS: 3.13 [1.25,7.84], p < .001; PFS: 2.54 [1.38, 4.68], p = .003). Conclusion The results of this umbrella meta-analysis first supported pre-existing understandings of the relationship between beneficial and adverse factors with the efficacy of ICI therapy. In addition, the overexpression of PD-L1 may adversely affect patients. Key Messages The umbrella meta-analysis first supported pre-existing understandings of the relationship between beneficial and adverse factors with the efficacy of immune checkpoint inhibitor therapy. This study found three factors that are not conducive to the efficacy of immune checkpoint inhibitor: epidermal growth factor receptor mutations, with liver metastases and antibiotics. We found the overexpression of PD-L1 may adversely affect patients.