Management of Endocrine and Metabolic Toxicities of Immune-Checkpoint Inhibitors: From Clinical Studies to a Real-Life Scenario

SIMPLE SUMMARY: Immune checkpoint inhibitors currently represent the standard of care for the treatment of different tumor types and have also been proven to be effective in several disease settings. However, their use is associated with a peculiar toxicity profile, related to the enhancement of the immune response, affecting several organs. The identification of predictive biomarkers has a crucial importance to select those patients that can better benefit from immunotherapy, improving their outcomes, while potentially avoiding toxicities with these drugs. In this review we will include the most recent data and current knowledge on immune-related endocrine and metabolic adverse events and on biomarkers and risk factors with a notable predictive value for their incidence. Furthermore, we will summarize the latest studies and recommendations on the clinical approach to these types of adverse events with the purpose of optimizing the diagnostic algorithm and their therapeutic management. ABSTRACT: Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape of solid tumors. However, although ICIs are better tolerated than conventional chemotherapy, their use is associated with a peculiar toxicity profile, related to the enhancement of the immune response, affecting several organs. Among immune-related adverse events (irAEs), up to 10% involve the endocrine system. Most of them are represented by thyroid disorders (hypothyroidism and hyperthyroidism), mainly correlated to the use of anti-PD-1 and/or anti-PD-L1 agents. Less common endocrine irAEs include hypophysitis, adrenalitis, and metabolic irAEs. A deeper understanding of endocrine toxicities is a critical goal for both oncologists and endocrinologists. A strict collaboration between these specialists is mandatory for early recognition and proper treatment of these patients. In this review we will provide a comprehensive overview of endocrine and metabolic adverse events of ICIs, with particular interest in the pathogenesis, predisposing factors and clinical presentation of these irAEs, and their impact on clinical outcomes of patients. Furthermore, we will summarize the most recent studies and recommendations on the clinical approach to immune-related endocrinopathies with the purpose to optimize the diagnostic algorithm, and to help both oncologists and endocrinologists to improve the therapeutic management of these unique types of irAEs, in a real-life scenario.