Efficacy and safety of osilodrostat in patients with ectopic Cushing´s syndrome. a real-world study in Spain

To evaluate the efficacy and safety of osilodrostat in patients with Ectopic Cushing syndrome (ECS). A retrospective, multicenter, real-world study of patients with ECS treated with osilodrostat. The main efficacy endpoint was the proportion of patients who were complete responders (urinary free cortisol [UFC] < the upper limit of normal [ULN] or adrenal insufficiency development). A total of 17 patients with ECS were identified. Most of the cases (88.2%, n = 15) were classified as severe Cushing´s syndrome (UFC > 5 ULN). Two patients received osilodrostat as first-line therapy, 9 as second line and 6 as a third line. Fourteen patients were treated with osilodrostat in monotherapy and 3 in combination with other treatments. The initial doses of osilodrostat ranged between 4 and 30 mg/day and the maximum doses between 4 and 60 mg/day. Response to osilodrostat was evaluated in 16 patients because one patient died few days (< 30) after the initiation of the treatment. We found that 88% (n = 14/16) were complete responders while 2 patients had partial response (UFC reduction > 50% but with no normalization). The median time to achieve hypercortisolism control was 4.5 weeks (range 1–12), and 40% of the cases had normal UFC after 1 month of treatment. Six patients developed adverse events associated with the use of osilodrostat: 3 had adrenal insufficiency, 1 QT prolongation and 1 deterioration of blood pressure control. Overall, osilodrostat controls hypercortisolism in approximately 90% of the patients with ECS and severe hypercortisolism and with normalization of UFC in 40% of cases after just 4 weeks of treatment. Therefore, osilodrostat should be considered as first-line treatment in patients with ECS, especially in patients with severe hypercortisolism. Several phase II and III clinical trials have proved the efficacy of osilodrostat in patients with Cushing´s disease, reporting UFC normalization in 70 to 90% of the cases. However, few data exist about real-world efficacy of osilodrostat. In addition, to best of our knowledge, no previous study has evaluated the efficacy and safety of osilodrostat in patients with Ectopic Cushing´s syndrome (ECS) in the Spanish population. Thus, in this multicenter study we evaluated the efficacy and safety of osilodrostat for the treatment of hypercortisolism in patients with ECS in our country. We enrolled 17 patients with ECS and 88.2% had severe Cushing´s syndrome. We found that 88% were complete responders while 2 patients had partial response (UFC reduction > 50% but with no normalization).