Endocrine toxicities in immune checkpoint inhibitors and tyrosine kinase inhibitors combined treatment: from clinical trials to real-life practice

Combination therapies with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) have revolutionized the landscape of cancer treatment, improving the quality of life and overall survival of patients. A deep knowledge of the side effects of ICIs and TKIs combination therapy is mandatory to ensure patient compliance and improve clinical outcomes. Both ICIs and TKIs may cause endocrinopathies such as thyroid dysfunction, adrenal insufficiency, hypophysitis, and diabetes mellitus. To avoid life-threatening conditions and improve patient’s compliance and outcomes, an early diagnosis of endocrine toxicity should be achieved and a multidisciplinary approach involving both endocrinologists and oncologists may be beneficial. This review specifically examines the endocrine adverse events reported in the clinical trials of ICI plus TKI combined treatment, their underlying mechanisms, and practical management guidelines.