Endocrine Abstracts

Introduction: The large, randomized, phase III study of pasireotide in Cushing’s disease found that pasireotide treatment resulted in rapid and sustained decreases in UFC levels and in significant improvements in signs and symptoms over 12 months of treatment. A 12-month extension of this trial has recently completed, and the results are reported here.

Methods: Patients with persistent/recurrent or de novo (if not surgical candidates) Cushing’s disease and UFC levels ≥1.5 times the upper limit of normal (ULN) were randomized to pasireotide 600 μg (n=82) or 900 μg (n=80) SC bid. Patients who had mean UFC≤ULN at month 12 or who were achieving clinical benefit from pasireotide were eligible to enter an additional 12-month extension. Dose titration was permitted at the investigator’s discretion (min: 300 μg SC bid; max: 1200 μg SC bid). UFC, serum cortisol and plasma ACTH were recorded every 3 months during the extension.

Results: Fifty-eight patients entered the extension, and only these patients are included in the analyses below. A mean decrease in UFC of 54.7% (95% CI: −71.8, −37.6) was observed from baseline to month 12, which was sustained throughout the extension phase; mean decreases of 55.7% (95% CI: −71.1, −40.3) and 59.5% (95% CI: −68.6, −50.5) were seen at months 18 and 24, respectively. Using a last observation carried forward analysis, 34.5% of patients had UFC≤ULN at month 24. A significant decrease from baseline in mean serum cortisol was observed at month 12 (−15.5%; 95% CI: −22.4; −8.6) and at month 24 (−17.8%; 95% CI: −26.9; −8.7). A similar trend was observed for plasma ACTH, with a reduction from baseline to month 12 of 16.2% (95% CI: −29.1, −3.4) and to month 24 of 13.9% (95% CI: −25.5, −2.2). Adverse events (AEs) during the extension phase were consistent with those reported during the core study and were predominantly gastrointestinal and hyperglycemia related. Further safety results are reported in a separate abstract (Bertherat et al.).

Conclusion: Long-term pasireotide use resulted in sustained improvements in UFC, serum cortisol and plasma ACTH over 24 months. These results support the use of pasireotide as a long-term treatment for Cushing’s disease in responsive patients.

Declaration of interest: I fully declare a conflict of interest. Details below:

Funding: This work was supported, however funding details unavailable.