Does development of iraes suggest improved cancer treatment outcomes compared with nondevelopment of IRAEs? Some data suggest that the occurrence of an IRAE predicts a better cancer response to ICPI treatment. The hypothesis is that the occurrence of an IRAE reflects better activation of the immune system. A meta-analysis with nivolumab in the treatment of …
How relatively likely are other endocrinopathies when comparing different classes of ICPIs? Patients on PD-1 inhibitors are about twice as likely to develop hypothyroidism as patients on ipilimumab. PD-1 inhibitor therapy is about five times more likely to cause hyperthyroidism compared with PD-L1 inhibitor therapy, but hypothyroidism rates are similar. Patients on ipilimumab are about …
What is the most frequently reported adverse event with PD-1 and PD-L1 inhibitors? Fatigue is the most commonly reported AE with these agents, and the pathogenesis is poorly understood. Individual drug studies report fatigue in 16% to 37% of patients on PD-1 inhibitors and 12% to 24% of patients on PD-L1 inhibitors. Of the patients …
What other endocrinopathies have been seen with ICPIs? Primary adrenal insufficiency, type 1 diabetes mellitus, and hypoparathyroidism have been occasionally seen with use of ICPIs. Primary adrenal insufficiency should be suspected in the setting of typical symptoms of adrenal insufficiency (fatigue, light headedness, weight loss, abdominal pain, nausea, vomiting), with an elevated plasma adrenocorticotropic hormone …
What other thyroid abnormalities can be seen in patients on ICPIs? Finally, normal or mildly low serum TSH levels along with normal or low free T 4 and frankly low total T 3 values suggest the nonthyroidal illness syndrome (euthyroid sick syndrome). These patients should not be given thyroid supplementation but, rather, should have their thyroid laboratory values monitored.
How should hyperthyroidism be managed in the setting of ICPI therapy? Patients with destructive thyroiditis who are asymptomatic can be monitored, and those with significant symptoms (palpitations, tremors) can be treated with beta-blockers and, if necessary, steroids. If and when patients convert to a hypothyroid phase, asymptomatic patients can be monitored with serial thyroid laboratory …
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How should hypothyroidism be monitored and managed in the setting of ICPI therapy? Monitoring for and treatment of these toxicities is critically important. The American Society of Clinical Oncology (ASCO) recommends measuring serum TSH and free T 4 levels every 4 to 6 weeks as part of routine clinical monitoring or for case detection in symptomatic patients …
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