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.