Long-term medical treatment of cushing's disease with pasireotide: a review of current evidence and clinical experience.

Cushing's disease is a rare condition of chronic hypercortisolism caused by an adrenocorticotropic hormone-secreting pituitary adenoma and associated with debilitating complications and excess mortality. Transsphenoidal adenomectomy is generally first-line treatment but is contraindicated in some patients and associated with significant post-surgical recurrence. While there are few data to support long-term use of most pharmacologic treatments, pasireotide (a multireceptor-targeted somatostatin analog) recently demonstrated sustained benefit in a 12-month, multicenter, Phase III trial and in 2 long-term extension studies. The Phase III trial (N=162) demonstrated reductions in urinary free cortisol in most patients, with durable treatment effect over 12 months. Biochemical improvement was generally paralleled by reductions in Cushing's-related signs and symptoms and enhanced health-related quality of life. Long-term treatment was evaluated in 58 patients who entered a planned 12-month extension phase. Reductions in urinary free cortisol remained stable throughout the extension, with further improvements noted in clinical signs and symptoms. Similar results were reported in the smaller Phase II extension (N=18; median treatment duration, 9.7 months; range, 2 months-4.8 years). Case reports have recently emerged demonstrating sustained disease control for upto 7 years in some patients. Safety considerations for long-term medical treatment with pasireotide are generally similar to those for other somatostatin analogs, except for the incidence and severity of hyperglycemia. Most patients experience new or worsening hyperglycemia with pasireotide treatment. Expert recommendations for treatment of pasireotide-associated hyperglycemia have recently been published and new studies are planned to elucidate the optimal treatment approach for pasireotide-associated hyperglycemia.