title: Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study.
abstract: BACKGROUND
  Many 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.
  
  
  METHODS
  Patients 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.
  
  
  RESULTS
  Twelve 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.
  
  
  CONCLUSIONS
  Pasireotide LAR is a promising treatment option for patients with acromegaly inadequately controlled with the first-generation somatostatin analogue octreotide LAR.
  
  
  BACKGROUND
  clinicaltrials.gov, NCT00600886 . Registered 14 January 2008.
authors.affiliation: Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Marcello D
authors.initials: MD
authors.lastname: Bronstein
authors.affiliation: Department of Medicine and Neurological Surgery, Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Fleseriu
authors.affiliation: Department of Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Neggers
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Naples, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Sheppard
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.affiliation: 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.
authors.forename: Chiung-Chyi
authors.initials: CC
authors.lastname: Shen
authors.affiliation: Endocrine Unit, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mônica
authors.initials: M
authors.lastname: Gadelha
authors.affiliation: Brain Research Imaging Centre, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Farrall
authors.affiliation: Clinical Development, Novartis Pharmaceuticals Corporation, Florham Park, NJ, USA.
authors.forename: Karina
authors.initials: K
authors.lastname: Hermosillo Reséndiz
authors.affiliation: Clinical Development, Oncology Business Unit, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Ruffin
authors.affiliation: Clinical Development, Novartis Pharmaceuticals Corporation, Florham Park, NJ, USA.
authors.forename: YinMiao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medicine, Columbia University College of Physicians & Surgeons, William Black Medical Res. Building, Room 9-905, 650 W. 168th Street, New York, NY, 10032, USA. puf1@columbia.edu.
authors.forename: Pamela
authors.initials: P
authors.lastname: Freda
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000236:Adenoma / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018592:Cross-Over Studies; D057915:Drug Substitution / Q000706:statistics & numerical data; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C517782:pasireotide; D015282:Octreotide
keywords: Acromegaly; Crossover; Extension; Octreotide; Pasireotide