ATCT-30: HYPERGLYCEMIA INDUCED BY PASIREOTIDE IN PATIENTS WITH CUSHING'S DISEASE OR ACROMEGALY

BACKGROUND: Cushing's disease (CD) and acromegaly are characterized by excessive hormone production by secreting pituitary tumors, resulting in comorbidities such as impaired glucose metabolism. Pasireotide is a next-generation, multireceptor-targeted somatostatin analog approved for treatment of CD (subcutaneous [SC] injection) and acromegaly (long-acting release [LAR] formulation). In clinical studies of pasireotide, hyperglycemia-related adverse events (AEs) were frequently observed. However, differences in reported rates of hyperglycemia among various trials in CD and acromegaly were noted. Here, we review the incidence and highlight differences of pasireotide-induced hyperglycemia in CD and acromegaly. METHODS: We reviewed clinical trials evaluating pasireotide in patients with CD or acromegaly. RESULTS: The frequency of hyperglycemia-related AEs was lower in patients with acromegaly treated with pasireotide LAR (57.3%–67.0%) than in patients with CD treated with pasireotide SC (73.0%). Fewer patients with acromegaly treated with pasireotide LAR discontinued due to hyperglycemia-related AEs, as reported in 2 separate trials (C2305, 3.4%; C2402, 3.8%) and an interim analysis (ACCESS, 0%), than in patients with CD treated with pasireotide SC (6.0%). Hyperglycemia-related AEs occurred in 40.0% of patients with acromegaly treated with pasireotide SC, and 10.0% discontinued treatment because of hyperglycemia. CONCLUSIONS: In studies of pasireotide, the frequency of hyperglycemia-related AEs was lower in acromegaly trials than in the CD trial, regardless of drug formulation, suggesting that disease pathophysiology may play an important role in glucose metabolism. However, among patients with acromegaly, the SC formulation resulted in fewer hyperglycemia-related AEs, indicating that drug formulation may also affect glucose metabolism. Because the CD trial occurred before the acromegaly trials, the benefit of increased physician experience with pasireotide use should also be considered. Ongoing studies evaluating pasireotide LAR in patients with CD and management of pasireotide-induced hyperglycemia in patients with CD or acromegaly (ClinicalTrials.gov identifiers: NCT01374906 and NCT02060383, respectively) will address these key safety issues.