Pasireotide Monotherapy in Cushing's Disease: a single-centre experience with 5-year extension of Phase III trial

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 88-111-Cushing's Disease & Non-Functioning Hypothalamus-Pituitary Tumors
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-97
Jessica M. MacKenzie-Feder*1, Isabelle Bourdeau2, Sophie Vallette3, Hugues Beauregard2, Louis-Georges Ste-Marie4 and André Lacroix5
1Centre hospitalier de l'Université de Montreal (CHUM), Montreal, QC, Canada, 2CHUM, Montreal, QC, Canada, 3Hopital Notre-Dame du CHUM, Montreal, QC, Canada, 4CHUM - Hopital Saint-Luc, Montreal, QC, Canada, 5Centre hospitalier de l'Universite de Montreal, Montreal, QC, Canada
Introduction: A recent phase III randomized controlled trial (NCT00434148) showed efficacy of pasireotide 600 or 900 mcg sc bid in the treatment of 162 patients with Cushing’s disease (CD) (1). Responding patients were invited to participate in an extension phase of the protocol and a preliminary report indicated a sustained response in the subgroup completing 24 months of therapy (2). We report the experience of our center where four patients were enrolled in this study. Two full responders have now completed five years of pasireotide treatment with complete disease control.

Methods: The original trial protocol was described in detail previously (1). The open-label extension phase consisted of three-monthly visits with clinical, biochemical, and imaging evaluation. Pasireotide dose titration was performed by individual investigators. The four research charts at our centre were retrospectively analyzed.

Results: The four patients with persistent CD following pituitary surgery completed the first six months of the trial and three continued on to the second open-label 6-month phase. Two patients with baseline urinary free cortisol (UFC) 3.5 to 4.5 times the upper limit of normal had a rapid and sustained response to pasireotide and entered the extension phase after 12 months. They remain in complete clinical and biochemical disease remission and one patient now only requires 150 ug sc bid to maintain normal UFC. All 4 patients initially developed glucose intolerance or diabetes; however, the two patients in the extension phase were controlled initially only with metformin, and were later able to discontinue all diabetes pharmacotherapy while remaining euglycemic with diet modification. Additional adverse events included second degree atrioventicular block type 1 without QT prolongation in a patient with pre-existing sinus bradycardia, and symptomatic cholelithiasis requiring cholecystectomy in a second patient.

Conclusions: These results demonstrate that pasireotide can provide sustained normalization of UFC and clinical signs and symptoms of CD for up to five years of therapy.  In these patients, initial mild hyperglycemia required only metformin and could be controlled by diet alone during prolonged effective pasireotide treatment. Long-term monitoring for other potential adverse events is indicated.

(1)  Colao A, et al.   A 12-month Phase 3 study of pasireotide in Cushing's disease. N Engl J Med 366:914-924, 2012   (2)  Bertherat J et al. Endocr Rev 2012;33:abst SUN-734 and SUN-735

Disclosure: JMM: , unrestricted grant, , Unrestricted grant. SV: Investigator, Novartis Pharmaceuticals, Research Funding, Serono. AL: Investigator, Novartis Pharmaceuticals, Consultant, Novartis Pharmaceuticals, Editor, Up To Date. Nothing to Disclose: IB, HB, LGS

*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: Clinical trial supported by Novartis (NCT00434148)