TY - JOUR
T1 - Extended treatment of Cushing's disease with pasireotide
T2 - Results from a 2-year, Phase II study
AU - Boscaro, M.
AU - Bertherat, J.
AU - Findling, J.
AU - Fleseriu, M.
AU - Atkinson, A. B.
AU - Petersenn, S.
AU - Schopohl, J.
AU - Snyder, P.
AU - Hughes, G.
AU - Trovato, A.
AU - Hu, K.
AU - Maldonado, M.
AU - Biller, B. M.K.
N1 - Funding Information:
Conflict of interest A.T., G.H. and K.H. are employees of Novartis. M.M. was an employee of Novartis during this study but is now employed by Boehringer Ingelheim. M.B. has no financial relationship or commercial interest. J.B. has been an investigator and consultant for Novartis, Ipsen and HRA Pharma. J.F. served as a consultant for Novartis and Corcept Therapeutics. M.F. has received research grants from Novartis and Corcept Therapeutics and has been a consultant for and received honoraria from Novartis and Ipsen. A.B.A. has been an investigator and a consultant for Novartis. J.S. has received consulting fees from Novartis, and S.P. from Novartis, Pfizer and Ipsen. P.S. has served as a consultant for Novartis. B.M.K.B. has recently served as the investigator on studies with research grants from Novartis and Corcept Therapeutics to the Massachusetts General Hospital Neuroendocrine Unit and as a consultant to Novartis and HRA Pharma.
Funding Information:
Acknowledgments We thank Daniel Webber, Mudskipper Business Ltd, for medical editorial assistance with this manuscript. This study was funded by Novartis Pharma AG. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation.
PY - 2014/8
Y1 - 2014/8
N2 - In a previous 15-day, Phase II study of patients with de novo or persistent/recurrent Cushing's disease (core study), treatment with pasireotide 600 μg sc bid reduced urinary free cortisol (UFC) levels in 76 % of patients and normalized UFC in 17 %. The objective of this study was to evaluate the efficacy and safety of extended treatment with pasireotide. This was a planned, open-ended, single-arm, multicenter extension study (primary endpoint: 6 months). Patients aged ≥18 years with Cushing's disease who completed the core study could enter the extension if they achieved UFC normalization at core study end and/or obtained significant clinical benefit. Of the 38 patients who completed the core study, 19 entered the extension and 18 were included in the efficacy analyses (three responders, 11 reducers, four non-reducers in the core study). At data cut-off, median treatment duration in the extension was 9.7 months (range: 2 months to 4.8 years). At extension month 6, 56 % of the 18 patients had lower UFC than at core baseline and 22 % had normalized UFC. Of the four patients who remained on study drug at month 24, one had normalized UFC. Reductions in serum cortisol, plasma adrenocorticotropic hormone, body weight and diastolic blood pressure were observed. The most common adverse events were mild-to-moderate gastrointestinal disorders and hyperglycemia. Pasireotide offers a tumor-directed medical therapy that may be effective for the extended treatment of some patients with Cushing's disease.
AB - In a previous 15-day, Phase II study of patients with de novo or persistent/recurrent Cushing's disease (core study), treatment with pasireotide 600 μg sc bid reduced urinary free cortisol (UFC) levels in 76 % of patients and normalized UFC in 17 %. The objective of this study was to evaluate the efficacy and safety of extended treatment with pasireotide. This was a planned, open-ended, single-arm, multicenter extension study (primary endpoint: 6 months). Patients aged ≥18 years with Cushing's disease who completed the core study could enter the extension if they achieved UFC normalization at core study end and/or obtained significant clinical benefit. Of the 38 patients who completed the core study, 19 entered the extension and 18 were included in the efficacy analyses (three responders, 11 reducers, four non-reducers in the core study). At data cut-off, median treatment duration in the extension was 9.7 months (range: 2 months to 4.8 years). At extension month 6, 56 % of the 18 patients had lower UFC than at core baseline and 22 % had normalized UFC. Of the four patients who remained on study drug at month 24, one had normalized UFC. Reductions in serum cortisol, plasma adrenocorticotropic hormone, body weight and diastolic blood pressure were observed. The most common adverse events were mild-to-moderate gastrointestinal disorders and hyperglycemia. Pasireotide offers a tumor-directed medical therapy that may be effective for the extended treatment of some patients with Cushing's disease.
KW - Clinical trial
KW - Cushing's disease
KW - Pasireotide
KW - SOM230
KW - Somatostatin analogue
UR - http://www.scopus.com/inward/record.url?scp=84904134106&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904134106&partnerID=8YFLogxK
U2 - 10.1007/s11102-013-0503-3
DO - 10.1007/s11102-013-0503-3
M3 - Article
C2 - 23943009
AN - SCOPUS:84904134106
SN - 1386-341X
VL - 17
SP - 320
EP - 326
JO - Pituitary
JF - Pituitary
IS - 4
ER -