Study supports Isturisa as first-line ectopic Cushing’s treatment
Researchers: Real-world findings support data seen in clinical trials
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Treatment with Isturisa (osilodrostat) normalized cortisol levels in most people with ectopic Cushing’s syndrome, including those with severe disease, according to real-world data from Spain.
Normal cortisol levels were reached within a month of starting treatment in more than a third of patients (36%).
“Therefore, [Isturisa] should be considered as first-line treatment in patients with [ectopic Cushing’s syndrome], especially in patients with [high cortisol levels],” wrote the researchers, who noted that, despite the small number of participants and the retrospective study design, the findings support efficacy data observed in clinical trials. The study, “Efficacy and safety of osilodrostat in patients with ectopic Cushing´s syndrome. A real-world study in Spain,” was published in the Journal of Endocrinological Investigations.
Cushing’s syndrome is a group of disorders marked by abnormally high levels of the hormone cortisol, a condition known as hypercortisolism. Cortisol is produced by the adrenal glands, located above the kidneys. One of the most common forms of the syndrome, called Cushing’s disease, is caused by a tumor in the pituitary gland. These tumors produce excessive amounts of adrenocorticotropic hormone (ACTH), which stimulates cortisol production.
When excess ACTH is produced by tumors in other parts of the body, the condition is known as ectopic Cushing’s syndrome, which is often associated with more severe disease.
Isturisa is an oral therapy that lowers cortisol by blocking an enzyme involved in its production. It’s approved in the U.S. for Cushing’s disease and other forms of Cushing’s syndrome, including ectopic Cushing’s syndrome, where surgery isn’t an option or hasn’t been effective.
Evaluating Isturisa in ectopic Cushing’s
Clinical trials have shown that Isturisa is generally effective in reducing cortisol levels in patients with Cushing’s syndrome, but data on its real-world use remain limited. To address this gap, researchers in Spain retrospectively analyzed data from 17 people with ectopic Cushing’s syndrome who’d been treated with Isturisa at multiple centers.
“In addition, to the best of our knowledge, no previous study has evaluated the efficacy and safety of [Isturisa] in patients with [ectopic Cushing’s syndrome] in the Spanish population,” they wrote.
The participants were a median age of 57.6, with 10 of them being women. Most ACTH-producing tumors were located in the lungs, while others arose in the pancreas, thymus, thyroid gland, or other sites. The tumor’s source couldn’t be identified in some cases.
Before starting Isturisa, most had already undergone surgery and/or been treated with other cortisol-lowering medications, with only two receiving Isturisa as a first-line therapy. Most (82.4%) received Isturisa alone, while 17.6% were treated in combination with other drugs.
Initial daily doses of Isturisa ranged from 4 to 30 mg per day. The median maintenance dose at the last follow-up visit was 9 mg per day, with wide variation between patients.
On average, patients had been living with the disease for about 10.7 months before starting Isturisa, and the median treatment duration at the time of the analysis was 3.5 months.
At the study’s start, most participants (88.2%) had severe disease, with urinary free cortisol (UFC) levels — a standard measure of cortisol production — more than five times the upper limit of normal.
With Isturisa, 88% of patients experienced a return to normal cortisol levels. This group also included three who eventually developed adrenal insufficiency, a condition that occurs when cortisol production is fully suppressed or very low. The treatment’s response was evaluated in 16 patients, as one died shortly after starting therapy.
Improvements were seen as early as one month, with more than one-third (36%) of patients reaching normal UFC levels. By three months, 90% of patients with available data had UFC levels within the normal range.
Isturisa was generally well tolerated. Six patients had treatment-related side effects, most commonly adrenal insufficiency, but none discontinued treatment due to side effects. Six died during follow-up due to tumor progression or disease-related complications not related to Isturisa.
“Considering [Isturisa] efficacy and the severity of [ectopic Cushing’s syndrome] … [Isturisa] should be considered as a first-line therapy in these patients in order to reduce the risk of hypercortisolism complications and mortality,” the researchers wrote.
