Endocrine Adverse Reactions of Tyrosine Kinase Inhibitors in Combination With Immune Checkpoint Inhibitors.

Abstract

Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) were recognized to cause endocrine adverse reactions (EARs). However, combination therapy-associated EARs are still unclear. This was a retrospective study based on the FDA Adverse Event Reporting System. We identified 938 464 cases of all adverse events related to 3 types of treatments. A total of 22 275 cases were EARs and divided into TKIs (n = 9181), ICIs (n = 11 363), and TKIs + ICIs group (n = 1731). The incidence of EARs was the highest in TKIs + ICIs followed by the ICIs and TKIs group. The TKIs + ICIs group had a higher risk of hypothyroidism than the ICIs group [odds ratio (OR) 1.47, 95% confidence interval (CI) 1.28-1.69] and a lower risk compared to the TKIs group (OR 0.68, 95% CI 0.58-0.79). The TKIs + ICIs group presented a higher risk of type 1 diabetes mellitus compared to the TKIs group (OR 26.61, 95% CI 18.60-38.07) but a lower risk compared to the ICIs group (OR 0.63, 95% CI 0.47-0.84). The risk of hypoglycemia was approximately 2.77 times greater in the TKIs + ICIs group than in the ICIs group (OR 2.77, 95% CI 1.95-3.95) and was also higher in the TKIs group compared to the ICIs group (OR 3.44, 95% CI 2.93-4.03). Compared to the ICIs group, the TKIs + ICIs group did not display a higher risk of pituitary dysfunction and primary adrenal insufficiency. The mortality risk of the TKIs + ICIs group was comparable to the ICIs group but was significantly lower than the TKIs group. EARs were more common in TKIs + ICIs therapy. The distribution of EARs in different glands varied among combination therapy and monotherapy. Combination therapy-associated EARs did not increase the risk of mortality.