Efficacy and safety of osilodrostat in patients with ectopic Cushing´s syndrome. a real-world study in Spain
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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).
Authors: Marta Araujo-Castro, Rogelio Garcia-Centeno, Laura González Fernández, Alfonso Soto-Moreno, Rosa Camara, María Dolores Ollero García, Ana Irigaray Echarri, Paola Gracia, Eider Pascual-Corrales, Betina Biagetti, Andrés Cardona, Inmaculada González Molero, Andreu Simo-Servat, Fernando Guerrero-Perez, Rocío Villar-Taibo, Ignacio Bernabéu, Carmen Fajardo-Montañana, Cristina Novo-Rodríguez, Carmen Tenorio-Jimenéz, María Calatayud, María Dolores Moure Rodríguez, Fernando Cordido, Ana Castro, Lucía Manzano Valero, Miguel Paja, Jessica Goi, Anna Aulinas, Pablo Abellán, Pedro Iglesias, Felicia Alexandra Hanzu
Institutions: Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Hospital General Universitario Gregorio Marañón, Hospital Universitario Virgen del Rocío, Hospital Universitari i Politècnic La Fe, Hospital Royo Villanova, Vall d'Hebron Hospital Universitari, Hospital Regional Universitario de Málaga, Bellvitge University Hospital, Complejo Hospitalario Universitario de Santiago, Hospital de La Ribera, Hospital Universitario Virgen de las Nieves, Hospital Universitario 12 De Octubre, Hospital de Cruces, Universidade da Coruña, Complexo Hospitalario Universitario A Coruña, Complejo Hospitalario Universitario de Toledo, Hospital Universitario de Toledo, University of the Basque Country, Hospital de Basurto, Hospital de Sant Pau, Centre for Biomedical Network Research on Rare Diseases, Institut de Recerca Sant Pau, Universidad Cardenal Herrera CEU, Hospital General Universitari de Castelló, Hospital Universitario Puerta de Hierro Majadahonda, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
OpenAlex ID: W4416936865