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Endocrine Adverse Reactions of Tyrosine Kinase Inhibitors in Combination With Immune Checkpoint Inhibitors
Wen Shao1, Kaiwei Yang2, Difei Lu1
1Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.
The Journal of Clinical Endocrinology and Metabolism
|February 22, 2025
Summary
Combination therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) increases endocrine adverse reactions (EARs). However, this combination therapy did not elevate mortality risk compared to monotherapy.
Area of Science:
- Oncology
- Pharmacology
- Endocrinology
Background:
- Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) are known to cause endocrine adverse reactions (EARs).
- The specific risks of EARs associated with the combination of TKIs and ICIs remain unclear.
Purpose of the Study:
- To investigate the incidence and types of endocrine adverse reactions (EARs) associated with tyrosine kinase inhibitor (TKI) monotherapy, immune checkpoint inhibitor (ICI) monotherapy, and combination therapy (TKIs+ICIs).
- To compare the risks of specific EARs, including hypothyroidism, type 1 diabetes mellitus, hypoglycemia, pituitary dysfunction, and primary adrenal insufficiency, across these treatment groups.
Main Methods:
- Retrospective analysis of 938,464 adverse event cases from the FDA Adverse Event Reporting System.
- Identification and categorization of 22,275 endocrine adverse reaction (EAR) cases into TKI (n=9,181), ICI (n=11,363), and TKI+ICI (n=1,731) groups.
- Statistical comparison of EAR incidence and specific endocrine event risks between monotherapy and combination therapy groups.
Main Results:
- The incidence of EARs was highest in the TKI+ICI group, followed by the ICI and TKI groups.
- The TKI+ICI group showed a higher risk of hypothyroidism and type 1 diabetes mellitus compared to the TKI group, but a lower risk compared to the ICI group for type 1 diabetes mellitus.
- The TKI+ICI group had a significantly higher risk of hypoglycemia compared to the ICI group, and a higher risk than the TKI group.
- No increased risk of pituitary dysfunction or primary adrenal insufficiency was observed in the TKI+ICI group compared to the ICI group.
- Mortality risk in the TKI+ICI group was comparable to the ICI group but significantly lower than the TKI group.
Conclusions:
- Endocrine adverse reactions are more frequent with combination therapy (TKIs+ICIs) than with monotherapy.
- The pattern of endocrine adverse reactions varies between combination and monotherapy, affecting different endocrine glands distinctly.
- Combination therapy with TKIs and ICIs does not appear to increase the risk of mortality.
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