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

Abstract

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.

Sintilimab-Induced Diabetic Ketoacidosis in a Patient with Radiation and Multichemorefractory Penile Cancer: A Case Report and Literature Review

“…Thus, novel molecular and immunotherapeutic targets are actively being sought [ 7 , 9 ]. Targeted therapies and ICIs are expected to play a role in advanced penile carcinoma [ 8 , 10 ]. However, there are no published randomized clinical trials on patients with distant metastatic disease who have already received standard chemotherapy, due to the rarity of PSCC [ 8 ].…”

Sintilimab-Induced Diabetic Ketoacidosis in A Patient with Radiation and Multichemorefractory Penile Cancer: A Case Report and Literature Review

“…Thus, novel molecular and immunotherapeutic targets are actively being sought [5,7]. Targeted therapies and immune checkpoint inhibitors are expected to play a role in advanced penile carcinoma [6,8]. However, there is no published randomized clinical trials for patients with distant metastatic disease who have already received standard chemotherapy, due to the rarity of penile SCC [6].…”

Adverse Effects of Immune-Checkpoint Inhibitors: A Comprehensive Imaging-Oriented Review

“…However, if suspected, hormones should be measured and the programmed dose of ICI should be withheld. Moreover, an MRI should always be performed to confirm diagnosis and exclude mimickers, such as metastasis and pituitary adenoma [71,72].…”

“…Incidence of ICI-related adrenalitis is reported to be less than 5% in patients treated with Nivolumab or Pembrolizumab [62,72,74].…”

“…Hyperglycemia may also occur after corticosteroids administration, commonly used to treat some irAEs, such as pneumonitis or enterocolitis [72].…”