Efficacy and safety of osilodrostat in patients with ectopic Cushing's syndrome

To analyze the efficacy and safety of osilodrostat in patients with ectopic Cushing's syndrome (ECS) in real-world studies.

A scoping review focused on the treatment with osilodrostat for patients with ECS was conducted in MEDLINE (PubMed) and Scopus databases. The review was conducted following the Joanna Briggs Institute protocol for scoping reviews.

A total of 12 articles with 46 patients (24 males and 22 females) with ECS were included. The age range was 11-85 years. Up to 70% had hyperglycemia, 82% hypertension, and 93% hypokalemia at the time of the ECS diagnosis. Severe hypercortisolism (urinary free cortisol (UFC) levels ≥ 5 times the upper limit of normal) was noted in 89% of patients. Osilodrostat was used as a first-line therapy in 44% (n = 20/46) and monotherapy in 74%. Most common osilodrostat initial doses were 2 or 4 mg/day (range 2-60 mg/day) and the maximum doses employed ranged between 2 and 100 mg/day. Block and replace (B&R) was used in 19 patients, titration in 15, and titration followed by B&R in 12 cases. Overall, 87% of the cases normalized UFC (90% (n = 18/20) when osilodrostat was used as first-line in monotherapy, 86.7% (n = 13/15) as a second-line in monotherapy, and 81.8% (n = 9/11) when used in combination with other drugs. The most common adverse event (AE) was adrenal insufficiency and no cases of hypokalemia worsening were reported.

Based on available real-world reports, osilodrostat appears to be a promising and fast-acting option for controlling severe hypercortisolism in ECS, with a generally acceptable safety profile. However, clinicians should closely monitor for adrenal insufficiency, particularly during dose titration.