Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study

BMC Endocrine Disorders

Research Article

Andrew J. Farrall¹  Michael Sheppard²  YinMiao Chen³  Karina Hermosillo Reséndiz³  Matthieu Ruffin⁴  Feng Gu⁵  Maria Fleseriu⁶  Pamela Freda⁷  Sebastian Neggers⁸  Chiung-Chyi Shen⁹  Annamaria Colao^1,10  Mônica Gadelha^1,11  Marcello D. Bronstein^1,12 

[1] Brain Research Imaging Centre, University of Edinburgh, Edinburgh, UK;Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Edgbaston, Birmingham, UK;Clinical Development, Novartis Pharmaceuticals Corporation, Florham Park, NJ, USA;Clinical Development, Oncology Business Unit, Novartis Pharma AG, Basel, Switzerland;Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Beijing, China;Department of Medicine and Neurological Surgery, Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA;Department of Medicine, Columbia University College of Physicians & Surgeons, William Black Medical Res. Building, Room 9-905, 650 W. 168th Street, 10032, New York, NY, USA;Department of Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands;Department of Minimally Invasive Skull Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan;Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan;Department of Physical Therapy, Hungkuang University, Taichung, Taiwan;Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Naples, Italy;Endocrine Unit, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School, São Paulo, Brazil;

关键词: Pasireotide;    Octreotide;    Acromegaly;    Extension;    Crossover;   

DOI  :  10.1186/s12902-016-0096-8

 received in 2015-07-14, accepted in 2016-03-14,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMany patients with acromegaly do not achieve biochemical control with first-generation somatostatin analogues. A large, multicenter, randomized, Phase III core study demonstrated that pasireotide LAR had significantly superior efficacy over octreotide LAR. This analysis explores the efficacy and safety of switching therapeutic arms in inadequately controlled patients during a 12-month crossover extension.MethodsPatients with inadequate biochemical control (GH ≥2.5 μg/L and/or IGF-1 > ULN) at end of core study (month 12) were eligible to switch to pasireotide LAR 40 mg/28 days (n = 81) or octreotide LAR 20 mg/28 days (n = 38). One dose escalation to pasireotide LAR 60 mg/28 days or octreotide LAR 30 mg/28 days was permitted, but not mandatory, at month 17 or 20.ResultsTwelve months after crossover, 17.3 % of pasireotide LAR and 0 % of octreotide LAR patients achieved GH <2.5 μg/L and normal IGF-1 (main outcome measure); 27.2 and 5.3 % of pasireotide LAR and octreotide LAR patients achieved normal IGF-1, respectively; 44.4 and 23.7 % of pasireotide LAR and octreotide LAR patients achieved GH <2.5 μg/L, respectively. Mean (±SD) tumor volume further decreased from the end of the core study by 25 % (±25) and 18 % (±28); 54.3 % of pasireotide LAR and 42.3 % of octreotide LAR patients achieved significant (≥20 %) tumor volume reduction during the extension. The safety profile of pasireotide LAR was similar to that of octreotide LAR, with the exception of the frequency and degree of hyperglycemia-related adverse events.ConclusionsPasireotide LAR is a promising treatment option for patients with acromegaly inadequately controlled with the first-generation somatostatin analogue octreotide LAR.Trial registrationclinicaltrials.gov, NCT00600886. Registered 14 January 2008

【 授权许可】

CC BY   
© Bronstein et al. 2016