ICEECE2012 Poster Presentations Pituitary Clinical (183 abstracts)
Introduction: Rapid and sustained decreases in UFC and significant improvements in signs and symptoms were seen in a large, randomized, 12-month phase III study of pasireotide in Cushings disease. The safety profile of pasireotide was found to be similar to that of other somatostatin analogues, with the exception of hyperglycemia-related AEs (reported in 72.8% of patients). This abstract reports safety data from a 12-month extension to this phase III trial.
Methods: Patients with persistent/recurrent or de novo (if not surgical candidates) Cushings disease and UFC levels ≥1.5xULN were randomized to pasireotide 600 μg (n=82) or 900 μg (n=80) sc bid. Patients who had mean UFC≤ULN or were achieving clinical benefit from pasireotide at month 12 (end of core) were eligible to enter the extension. Dose titration was permitted at the investigators discretion (min: 300 μg sc bid; max: 1200 μg sc bid). Data on AEs were collected throughout the extension.
Results: Fifty-eight patients entered the extension phase and 19 discontinued prior to month 24. After 24 months pasireotide treatment, UFC was decreased by a mean of 59.5% (95% CI: −68.6, −50.5). During the core and extension phases, 98.1% of patients experienced≥1 AE, and 25.9% experienced≥1 SAE. There were no deaths. The safety profile in the extension phase was similar to that in the core; the majority of reported AEs were mild-to-moderate GI events. During the 24-month treatment period, 40.1% and 29.6% of patients had an AE of hyperglycemia and diabetes mellitus respectively. Mean HbA1c increased from 5.8% at baseline to 7.2, 6.8 and 6.8% at months 12, 18 and 24 respectively. In addition to the patients who reported these events during the core study, 2 additional patients experienced SAEs during the extension, 3 reported mild-to-moderate cholelithiasis, one reported a newly occurring QTcF >480 ms, and 2 had a >30 ms increase in QTcF. Three patients discontinued because of an AE during the extension. Further 24-month efficacy results are reported in a separate abstract (Schopohl et al.).
Conclusion: The long-term safety profile of pasireotide was similar to that reported following 12 months pasireotide treatment, including the proportion of patients with hyperglycemia-related AEs. These results support the use of pasireotide as a long-term treatment for Cushings disease.
Declaration of interest: I fully declare a conflict of interest. Details below:
Funding: This work was supported, however funding details unavailable.