Oettle, Matthias

Abstract Context Most of the patients included in the clinical trials and real-world studies with osilodrostat only include patients with adrenocorticotropic hormone dependent Cushing syndrome (CS), while data on the efficacy and safety of osilodrostat in patients with adrenal CS is scarce. Objective To assess the efficacy and safety of osilodrostat in adrenal CS. Methods International study of patients with adrenal CS: patients treated with osilodrostat at any time were enrolled in the safety evaluation and those treated for longer than 4 weeks, in the efficacy evaluation. Patients were classified as responders if they experienced a reduction in urinary free cortisol (UFC) >50% (complete responders when UFC levels were below the upper limit of normal [ULN] and partial responders if there was a reduction >50% but not normalization). Results Twenty-eight patients with adrenal CS were enrolled: 16 with adrenocortical carcinoma and 12 with benign disease. Osilodrostat was used in monotherapy in 22 patients and in combination with metyrapone in 6 cases. In those patients treated for longer than 4 weeks (n = 21), 66.7% were classified as responders (28.6% with complete response and 38.1% with partial response), and for those treated for longer than 12 weeks, the rate of response increased to 87.5% The use of osilodrostat as a nonfirst-line therapy (odds ratio 15.0, P = .010) was a predictor of response. Osilodrostat led to a significant decrease in systolic blood pressure and body weight (P < .05). Nine patients developed one or more adverse events and in 56% (n = 5) led to osilodrostat discontinuation. Conclusion Osilodrostat controls hypercortisolism in 66.7% of patients with adrenal CS treated for longer than 4 weeks and in 87.5% of cases treated for longer than 12 weeks, with a positive impact on blood pressure and body weight. Patients who received osilodrostat after other previous steroidogenesis inhibitors have a higher probability of response.