Endocrine Abstracts

Background: Dopamine and somatostatin receptors on corticotroph pituitary adenomas are targets for medical treatment of Cushing’s disease (CD). Data indicate synergistic effects between pasireotide and cabergoline in improving biochemical control rates and clinical features in patients with CD.

Objective: To evaluate safety and efficacy of pasireotide alone or with cabergoline in patients with CD.

Methods: Patients: adults with confirmed diagnosis of CD (persistent/recurrent/de novo not considered candidates for pituitary surgery). Group 1: pasireotide-naïve patients or who had discontinued pasireotide earlier for lack of efficacy; Group 2: patients currently receiving MTD of pasireotide monotherapy for ≥8 weeks, but biochemically uncontrolled (mean UFC (mUFC)>ULN; mean of three samples with 2/3>ULN). Design: phase II, multicenter, prospective, international, open-label, non-comparative. Target enrollment=128 (Group 1=68; Group 2=60). Treatment (stepwise): Group 1: pasireotide s.c. 600 μg bid for 8 weeks; if uncontrolled, dose increased to 900 μg bid for 8 weeks; if uncontrolled, pasireotide s.c. 900 μg bid+cabergoline 0.5 mg qd for 8 weeks (if intolerant of pasireotide 900 μg bid, 600 μg bid allowed); if uncontrolled, cabergoline dose increased to 1 mg qd for 8 weeks. Group 2: pasireotide (300/600/900 μg bid) s.c.+cabergoline 0.5 mg qd for 8 weeks; if uncontrolled, cabergoline dose increased to 1 mg qd for 8 weeks. For both groups, dose modifications for cabergoline due to safety are allowed. Endpoints: primary: proportion of responders (mUFC≤1.0×ULN) in i) Group 1: with pasireotide alone or with cabergoline at wk35 ii) Group 2: with pasireotide+cabergoline at wk17. Secondary: actual and percentage change in mUFC from baseline to study end; proportion of patients attaining mUFC≤1.0×ULN, proportion of UFC responders or patients having ≥50% reduction from baseline in mUFC at each scheduled visit; shift from baseline in clinical signs. No formal hypothesis testing planned. Proportion of patients (95% CI) attaining primary endpoint will be reported.

Conclusions: This study will assess safety and efficacy of pasireotide in combination with cabergoline as a stepwise approach in the treatment of CD.