title: Pasireotide versus octreotide in acromegaly: a head-to-head superiority study.
abstract: BACKGROUND
  Biochemical control reduces morbidity and increases life expectancy in patients with acromegaly. With current medical therapies, including the gold standard octreotide long-acting-release (LAR), many patients do not achieve biochemical control.
  
  
  OBJECTIVE
  Our objective was to demonstrate the superiority of pasireotide LAR over octreotide LAR in medically naive patients with acromegaly.
  
  
  METHODS
  We conducted a prospective, randomized, double-blind study at 84 sites in 27 countries.
  
  
  METHODS
  A total of 358 patients with medically naive acromegaly (GH >5 μg/L or GH nadir ≥1 μg/L after an oral glucose tolerance test (OGTT) and IGF-1 above the upper limit of normal) were enrolled. Patients either had previous pituitary surgery but no medical treatment or were de novo with a visible pituitary adenoma on magnetic resonance imaging.
  
  
  METHODS
  Patients received pasireotide LAR 40 mg/28 days (n = 176) or octreotide LAR 20 mg/28 days (n = 182) for 12 months. At months 3 and 7, titration to pasireotide LAR 60 mg or octreotide LAR 30 mg was permitted, but not mandatory, if GH ≥2.5μg/L and/or IGF-1 was above the upper limit of normal.
  
  
  METHODS
  The main outcome measure was the proportion of patients in each treatment arm with biochemical control (GH <2.5 μg/L and normal IGF-1) at month 12.
  
  
  RESULTS
  Biochemical control was achieved by significantly more pasireotide LAR patients than octreotide LAR patients (31.3% vs 19.2%; P = .007; 35.8% vs 20.9% when including patients with IGF-1 below the lower normal limit). In pasireotide LAR and octreotide LAR patients, respectively, 38.6% and 23.6% (P = .002) achieved normal IGF-1, and 48.3% and 51.6% achieved GH <2.5 μg/L. 31.0% of pasireotide LAR and 22.2% of octreotide LAR patients who did not achieve biochemical control did not receive the recommended dose increase. Hyperglycemia-related adverse events were more common with pasireotide LAR (57.3% vs 21.7%).
  
  
  CONCLUSIONS
  Pasireotide LAR demonstrated superior efficacy over octreotide LAR and is a viable new treatment option for acromegaly.
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia (A.C.), Università Federico II di Napoli, 80131 Naples, Italy; Neuroendocrine Unit (M.D.B.), Division of Endocrinology and Metabolism, University of São Paulo Medical School, 3858-Jardim Paulista, São Paulo, Brazil; Department of Medicine (P.F.), Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Endocrinology (F.G.), Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; Department of Neurosurgery (C.-C.S.), Taichung Veterans General Hospital, Taichung 40705, Taiwan; Department of Physical Therapy (C.-C.S.), Hungkuang University, Taichung 43302, Taiwan; Department of Medicine and Tri-Service General Hospital (C.-C.S.), National Defense Medical Center, Taipei 11490, Taiwan; Endocrine Unit (M.G.), Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 22421020, Brazil; Department of Medicine and Neurological Surgery (M.F.), Northwest Pituitary Center, Oregon Health and Science University, Portland, Oregon 97239; Department of Medicine (A.J.v.d.L.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands; Brain Research Imaging Centre (A.J.F.), University of Edinburgh, Edinburgh EH4 2XU, United Kingdom; Clinical Development (K.H.R., Y.C.), Novartis Pharmaceuticals Corporation, Florham Park, New Jersey 07932; Clinical Development (M.R.), Oncology Business Unit, Novartis Pharma AG, CH-4057 Basel, Switzerland; and Centre for Endocrinology, Diabetes, and Metabolism (M.S.), University of Birmingham, Edgbaston, Birmingham, B152TT.
authors.forename: A
authors.initials: A
authors.lastname: Colao
authors.forename: M D
authors.initials: MD
authors.lastname: Bronstein
authors.forename: P
authors.initials: P
authors.lastname: Freda
authors.forename: F
authors.initials: F
authors.lastname: Gu
authors.forename: C-C
authors.initials: CC
authors.lastname: Shen
authors.forename: M
authors.initials: M
authors.lastname: Gadelha
authors.forename: M
authors.initials: M
authors.lastname: Fleseriu
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
authors.forename: A J
authors.initials: AJ
authors.lastname: Farrall
authors.forename: K
authors.initials: K
authors.lastname: Hermosillo Reséndiz
authors.forename: M
authors.initials: M
authors.lastname: Ruffin
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Sheppard
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000209:etiology; D000236:Adenoma / Q000150:complications / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013004:Somatostatin; C517782:pasireotide; D015282:Octreotide