Introduction: Pasireotide reduced UFC levels in 22 of 29 patients with Cushings disease after 15 days treatment (Boscaro et al. JCEM 2009). Of these 22 patients, 5 achieved normalized UFC (UFC-responders) and 17 had reduced but not normalized UFC (UFC-reducers). Results of an extension phase to this study are presented.
Methods: Patients with de novo or persistent/recurrent Cushings disease received pasireotide 600 μg s.c. bid for 15 days in the core study. Patients with significant clinical benefit after 15 days could enroll in an open-ended extension study. Patients with normalized UFC at end-of-core were to receive pasireotide 600 μg bid, with dose titration to 900 μg bid if required. All other patients were to receive pasireotide 900 μg bid. Primary endpoint: UFC response at month 6.
Results: Nineteen patients entered the extension phase, three of whom were UFC-responders at end-of-core. Mean treatment duration was 16 months (2mo4.8y). Of 18 evaluable patients at 6 months, 10 (56%) had a reduction in UFC, of whom 4 (22%) were UFC-responders, and 6 (33%) were UFC-reducers. Of the 4 UFC-responders at 6 months, 1 was a UFC-responder and 2 were UFC-reducers at the end of the core study. In all patients, there was a trend toward a reduction in mean serum cortisol and plasma ACTH. Mean change in systolic blood pressure and bodyweight was −8.87 mmHg and −7.4 kg at 6 months. The most frequently reported AEs were diarrhea (13 patients), nausea (12 patients), hyperglycemia (11 patients), abdominal pain (9 patients). Most AEs were grade 1 or 2; 6 patients reported grade 3 hyperglycemia and 1 patient reported grade 4 diabetes.
Conclusion: Long-term pasireotide treatment resulted in >50% of patients achieving normalization or a reduction in UFC, and was generally well tolerated. These results suggest pasireotide may be an effective long-term pituitary targeted treatment for Cushings disease.