Endocrine Adverse Events Caused by Different Types and Different Doses of Immune Checkpoint Inhibitors in the Treatment of Solid Tumors: A Meta-Analysis and Systematic Review

The aim of this meta-analysis was to assess the risks of endocrine adverse events in patients with malignancies treated with different types and different doses of immune checkpoint inhibitors (ICIs). PubMed and Embase were searched for randomized controlled trials on ICIs and endocrine adverse events since 2000, and meta-analysis was carried out. Twenty-six randomized controlled trials comprising 13 824 patients with malignancies were included. Compared with the other tumor therapies (used as a control group), patients treated with programmed death-1 inhibitors appeared to be at higher risks of hypothyroidism, hyperthyroidism, thyroiditis, hypophysitis or hypopituitarism, and type 1 diabetes mellitus, while there was no difference in the risk of primary adrenal insufficiency. It was also found that patients treated with cytotoxic T-lymphocyte-associated protein-4 inhibitors were at higher risk of hypophysitis or hypopituitarism, primary adrenal insufficiency, and hypothyroidism. In comparison, patients treated with programmed death-ligand 1 inhibitors were at higher risk of hyperthyroidism and hypothyroidism. Compared with the control group, both low-dose and high-dose ICI groups were at higher risk of hypothyroidism and hyperthyroidism, and the low-dose group had increased risk of thyroiditis and primary adrenal insufficiency. There was no significant difference in the risk of type 1 diabetes between the low-dose group and the high-dose group. The risk of hypophysitis or hypopituitarism in the high-dose group (relative risk, 20.12; 95% confidence interval, 8.02-50.46) was significantly higher than that in the low-dose group (relative risk, 4.92; 95% confidence interval, 2.11-11.47). The risk of endocrine adverse events was increased in patients treated with ICIs. Different types and doses of ICIs have varying characteristics of endocrine adverse events.