Evaluation of Late-Night Salivary Cortisol during 12 Months of Pasireotide Treatment in Patients with Cushing's Disease

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

Poster Board MON-89
Beverly MK Biller*1, Stephan Petersenn2, Rosario Pivonello3, James W Findling4, Maria Fleseriu5, Andrew Trovato6, Gareth Hughes7, Monica Ligueros-Saylan8 and John Newell-Price9
1Massachusetts General Hospital, Boston, MA, 2ENDOC Center for Endocrine Tumors, Hamburg, Germany, 3UniversitÓ Federico II di Napoli, Naples, Italy, 4Medical College of Wisconsin, Milwaukee, WI, 5Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, 6Novartis Pharma AG, Basel, Switzerland, 7Novartis Pharmaceuticals Corporation, Florham Park, NJ, 8Novartis Pharmaceuticals Corporation, East Hanover, NJ, 9University of Sheffield, Sheffield, United Kingdom
Introduction: The measurement of salivary cortisol is a simple, convenient, accurate and reproducible technique with potential value during monitoring of patients with hypercortisolism. The current analysis reports changes in late-night salivary cortisol (LNSC) during pasireotide (Signifor®) treatment in patients with Cushing’s disease.

Methods: A 12-month, multicenter, Phase III study enrolled 162 adult patients with confirmed de novoor persistent/recurrent Cushing’s disease who were randomized to pasireotide 600 μg or 900 μg sc bid. Assessment of LNSC (assay: cortisol ELISA RE52611, IBL-Hamburg GmbH, Germany; limit of detection 0.41 nmol/L; intra-assay CV of 3.2–7.6% at 7.0–80.8 nmol/L, inter-assay CV of 6.2–9.1% at 5.9–72.8 nmol/L) was an exploratory objective based on a single, optional measurement at midnight ± 1 hour on the same day as one of the 24-hour urinary free cortisol (UFC) measurements. All samples were analyzed by the central laboratory. UFC control was defined as UFC ≤ULN, partial UFC control as UFC >ULN and ≥50% decrease from baseline.

Results: Baseline LNSC was measured in 93 patients; median levels were 17.3 and 10.3 nmol/L in the 600 μg (n=48) and 900 μg (n=45) dose groups (normal range 0.83–8.3). After 6 months there was a median decrease of 4.9 nmol/L (26.5%; mean –4.7 nmol/L [95% CI –44.8, 39.3]) and 2.4 nmol/L (41.8%; mean –27.9 nmol/L [95% CI –43.7, 34.0]) in the 600 μg and 900 μg groups, respectively. LNSC was normalized at 6 months in 25/67 (37.3%) patients with baseline LNSC above ULN, comprising 16/40 (40.0%) and 9/27 (33.3%) patients in the 600 μg and 900 µg groups, respectively. 10/25 patients with normalized LNSC at 6 months also had normalized UFC; seven had partial UFC control. Overall, there was a median LNSC decrease at 12 months of 7.2 nmol/L (42.2%; mean –9.6 nmol/L [95% CI –40.8, 18.3]) and 1.6 nmol/L (26.1%; mean –30.5 nmol/L [95% CI –41.1, 13.5]) in the 600 μg and 900 μg groups, respectively. In both groups, LNSC decreased in UFC controlled/partially controlled patients and increased in uncontrolled patients; patient numbers within each UFC control subgroup were low. An exploratory analysis demonstrated weak linear correlation (r=0.2), but moderate correlation (r=0.5) on the log scale between LNSC and UFC when all time points were pooled; at baseline, the linear correlation was strong (r=0.9).

Conclusions: Pasireotide decreased LNSC levels during 12 months of treatment. Salivary cortisol may be a simpler and more convenient biomarker than 24-hour UFC to assess hypercortisolism in patients with Cushing’s disease, although further studies are required.

Disclosure: BMB: Investigator, Novartis Pharmaceuticals, Consultant, Novartis Pharmaceuticals, Investigator, Corcept, Consultant, HRA Pharma. SP: Speaker, Novartis Pharmaceuticals, Medical Advisory Board Member, Novartis Pharmaceuticals, Speaker, Ipsen, Medical Advisory Board Member, Ipsen, Speaker, Pfizer, Inc., Medical Advisory Board Member, Pfizer, Inc.. RP: Advisory Group Member, Novartis Pharmaceuticals, Speaker, Novartis Pharmaceuticals, Investigator, Novartis Pharmaceuticals, Advisory Group Member, Ipsen, Speaker, Ipsen, Investigator, Ibsa, Investigator, Pro Strakan, Investigator, Viropharma, Medical Advisory Board Member, Viropharma, Consultant, Italfarmaco, Investigator, Pfizer, Inc., Medical Advisory Board Member, Pfizer, Inc.. JWF: Investigator, Corcept, Consultant, Corcept, Investigator, Novartis Pharmaceuticals, Consultant, Novartis Pharmaceuticals, Consultant, Abbott Laboratories. MF: Consultant, Novartis Pharmaceuticals, Consultant, Novartis Pharmaceuticals, Consultant, Ipsen, Consultant, Ipsen. AT: Employee, Novartis Pharmaceuticals. GH: Employee, Novartis Pharmaceuticals. ML: Employee, Novartis Pharmaceuticals. JN: Investigator, Novartis Pharmaceuticals, Consultant, Novartis Pharmaceuticals, Speaker, Novartis Pharmaceuticals.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Novartis funded editorial support provided by Mudskipper