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

## TL;DR

This study finds that PD-1/PD-L1 cancer immunotherapy is linked to a higher risk of serious neurological side effects compared to standard treatments.

## Contribution

The study is the first to highlight a significant increase in serious neurological adverse events with PD-1/PD-L1 inhibitors.

## Key findings

- PD-1/PD-L1 therapy showed a higher incidence of serious neurological adverse events compared to the control group.
- Six major neurological adverse events, including stroke and Guillain-Barré, were more common in the PD-1/PD-L1 group.
- The atezolizumab subgroup had a notably higher risk of serious neurological adverse events.

## Abstract

•A meta-analysis of 141 RCTs evaluated 12 PD-1/PD-L1 inhibitors in 18 cancer types.•PD-1/PD-L1 therapy has a higher incidence of serious Neurological Adverse Events (NAEs) compared to the control group.•Six predominant NAEs showed higher incidence in the PD-1/PD-L1 group, including stroke and Guillain-Barré.•This analysis reveals a potential interaction between cancer immunotherapy and the nervous system.

A meta-analysis of 141 RCTs evaluated 12 PD-1/PD-L1 inhibitors in 18 cancer types.

PD-1/PD-L1 therapy has a higher incidence of serious Neurological Adverse Events (NAEs) compared to the control group.

Six predominant NAEs showed higher incidence in the PD-1/PD-L1 group, including stroke and Guillain-Barré.

This analysis reveals a potential interaction between cancer immunotherapy and the nervous system.

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.

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.

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 (I2 = 16 %, p = 0.06).

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.