Background: Pasireotide is a multireceptor-targeted somatostatin analogue that predominantly binds to somatostatin receptor subtype 5 (SSTR5) and provides sustained control of urinary free cortisol (UFC) levels in some patients with Cushings disease (CD). Cabergoline is a dopamine D2 receptor agonist with efficacy in some patients with CD. Most corticotropinomas co-express SSTR5 and D2, providing rationale for combination treatment with pasireotide and cabergoline. Results are reported from a Phase II study of pasireotide alone or combined with cabergoline in patients with CD.
Methods: Open-label, multicentre, non-comparative study. Patients with persistent/recurrent or de novo (if not surgical candidates) CD who were pasireotide-untreated at screening were enrolled. Patients initiated treatment with pasireotide (subcutaneous) 0.6 mg bid. If mean UFC (mUFC; from two consecutive 24h collections) remained >ULN after 8 weeks, the pasireotide dose was increased, if tolerated, to 0.9 mg bid for 8 weeks. If mUFC remained elevated, cabergoline 0.5mg qd was added for 8 weeks, increasing to 1.0mg qd for another 8 weeks if mUFC>ULN. Primary endpoint: proportion of patients with mUFC≤ULN at week 35.
Results: Sixty-six patients (median 40.5 years; 59 females) were enrolled. Twenty-seven patients received pasireotide monotherapy; 39 received combination therapy. At week 35, mUFC≤ULN was achieved in 25 patients (37.9%, 95%CI 26.250.7), 13 of whom received pasireotide monotherapy, with a further 12 achieving the primary endpoint after cabergoline addition. The most common (>20%) AEs were hyperglycaemia (51.5%), nausea (47.0%), diarrhoea (45.5%), headache (28.8%), dizziness (24.2%) and cholelithiasis (24.2%). Sixteen (24.2%) patients discontinued before week 35 (10 on pasireotide monotherapy); seven (10.6%) because of AEs (five on pasireotide monotherapy). Two on-treatment deaths occurred, both unrelated to study treatment.
Conclusions: Pasireotide alone or combined with cabergoline effectively controlled mUFC. Results suggest that addition of cabergoline in patients with persistently elevated mUFC is an effective strategy to enhance the control of CD.
20 May 2017 - 23 May 2017