title: Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, Phase III study.
abstract: OBJECTIVE
  A large, randomized, double-blind, Phase III core study demonstrated that pasireotide LAR was significantly superior to octreotide LAR at providing GH <2.5 μg/L and normalized IGF-1 after 12 months' treatment in patients with acromegaly. We report the efficacy and safety of pasireotide LAR and octreotide LAR after up to 26 months' treatment.
  
  
  METHODS
  Patients with GH <2.5 μg/L and IGF-1 ≤1× ULN at month 12, or patients considered to be experiencing clinical benefit, were eligible to continue receiving their randomized therapy in the extension. Efficacy and safety in the pasireotide LAR and octreotide LAR groups were evaluated for up to 26 months.
  
  
  RESULTS
  Overall, 120 patients who completed the core study continued receiving pasireotide LAR (n = 74) or octreotide LAR (n = 46) in the extension. At month 25, biochemical control (GH <2.5 μg/L and normal IGF-1) was achieved by 48.6% (36/74) and 45.7% (21/46) of patients in the pasireotide LAR and octreotide LAR arms [60.8% (45/74) and 52.2% (24/46) when including patients with IGF-1 < LLN], respectively. In total, 74.7% of pasireotide LAR and 71.6% of octreotide LAR patients had tumor volume decrease ≥20% from baseline to month 26. Most AEs were mild or moderate. Hyperglycemia-related AEs were seen in 62.9 and 25.0% of pasireotide LAR and octreotide LAR patients, respectively. No new safety signals were observed in the extension compared with the core study.
  
  
  CONCLUSIONS
  GH and IGF-1 suppression is maintained for up to 25 months during pasireotide LAR treatment. The safety profile of pasireotide LAR is typical of a somatostatin analogue, except for the frequency and degree of hyperglycemia.
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK, m.c.sheppard@bham.ac.uk.
authors.forename: Michael
authors.initials: M
authors.lastname: Sheppard
authors.forename: Marcello D
authors.initials: MD
authors.lastname: Bronstein
authors.forename: Pamela
authors.initials: P
authors.lastname: Freda
authors.forename: Omar
authors.initials: O
authors.lastname: Serri
authors.forename: Laura
authors.initials: L
authors.lastname: De Marinis
authors.forename: Luciana
authors.initials: L
authors.lastname: Naves
authors.forename: Liudmila
authors.initials: L
authors.lastname: Rozhinskaya
authors.forename: Karina
authors.initials: K
authors.lastname: Hermosillo Reséndiz
authors.forename: Matthieu
authors.initials: M
authors.lastname: Ruffin
authors.forename: YinMiao
authors.initials: Y
authors.lastname: Chen
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000236:Adenoma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001938:Brazil; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009656:North America; D012074:Remission Induction; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D001786:Blood Glucose; C583557:IGF1 protein, human; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C517782:pasireotide
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