Neurological adverse events of PD-1/PD-L1 immune checkpoint inhibitors in clinical trials: A meta-analysis

PD-1/PD-L1免疫检查点抑制剂临床试验中神经系统不良事件:一项荟萃分析

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Abstract

OBJECTIVE: Based on the data in clinical studies, the authors explored the potential link between cancer immunotherapy and Neurological Adverse Events (NAEs), and established a clinical picture. METHODS: The authors searched PubMed, Embase, Cochrane Library, Web of Science databases, and ClinicalTrials.gov for Randomized Controlled Trials (RCTs) using PD-1/PD-L1 inhibitors for cancer until November 2023. A total of 141 articles were included, covering 12 PD-1/PD-L1 inhibitors and 18 cancer types. RESULTS: Finally, 90,079 patients of 141 RCTs met the eligibility criteria. Data showed no significant difference in the incidence of NAEs in patients receiving PD-1/PD-L1 inhibitors compared to the control group (OR = 1.07; 95 % CI 0.95, 1.21; p = 0.25). However, the authors surprisingly found that the incidence of serious NAEs in the PD-1/PD-L1 group was higher than the control group (OR = 1.34; 95 % CI 1.24, 1.44; p < 0.00001), the same with NAEs in atezolizumab subgroup (OR = 1.66; 95 % CI 1.08, 2.56; p = 0.02). It is worth noting that the intra-group heterogeneity of the serious NAEs subgroup was relatively small (I(2) = 16 %, p = 0.06). CONCLUSION: The authors first proposed the opinion that the incidence of serious NAEs in immunotherapy patients was significantly higher than in other groups, providing a novel direction for research.

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