title: Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial.
abstract: BACKGROUND
  Methodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the long-acting lanreotide formulation.
  
  
  OBJECTIVE
  The aim of the study was to better characterize the effects of primary lanreotide Autogel treatment on tumor size in patients with GH-secreting macroadenomas.
  
  
  METHODS
  PRIMARYS was a 48-week, multicenter, open-label, single-arm study.
  
  
  METHODS
  The study was conducted at specialist endocrine centers.
  
  
  METHODS
  Treatment-naïve acromegalic patients with GH-secreting macroadenomas participated in the study.
  
  
  METHODS
  Lanreotide Autogel 120 mg was administered sc every 28 days (without dose titration).
  
  
  METHODS
  The primary endpoint was the proportion of patients with clinically significant (≥20%) tumor volume reduction (TVR) at week 48/last post-baseline value available using central assessments from three readers. The null hypothesis (H0) for the primary endpoint was that the proportion with TVR was ≤55%. Secondary endpoints included: TVR at other time points, GH and IGF-1, acromegalic symptoms, quality of life (QoL), and safety.
  
  
  RESULTS
  Sixty-four of 90 (71.1%) patients completed the study. Clinically significant TVR at 48 weeks/last post-baseline value available was achieved by 62.9% (95% confidence interval, 52.0, 72.9) of 89 patients in the primary analysis (intention-to-treat population; H0 not rejected) and 71.9-75.3% in sensitivity (n = 89) and secondary analyses (n = 63) (H0 rejected). At 12 weeks, 54.1% had clinically significant TVR. Early and sustained improvements also occurred in GH and IGF-1, acromegalic symptoms, and QoL. No patients withdrew due to gastrointestinal intolerance.
  
  
  CONCLUSIONS
  Primary treatment with lanreotide Autogel, administered at 120 mg (highest available dose) without dose titration, in patients with GH-secreting macroadenomas provides early and sustained reductions in tumor volume, GH and IGF-1, and acromegalic symptoms, and improves QoL.
authors.affiliation: Department of Endocrinology and Metabolic Diseases (P.J.C.), Centre Hospitalier Universitaire Larrey, F-31059 Toulouse, France; Department of Endocrinology (J.S.B.), Aberdeen Royal Infirmary, Aberdeen AB25 2ZP, United Kingdom; ENDOC Center for Endocrine Tumors (S.P.), 20357 Hamburg, Germany; Department of Endocrinology (D.F.), Derriford Hospital, Plymouth PL6 8DH, United Kingdom; Department of Endocrinology, Diabetes, Metabolic Diseases, and Nutrition (A.T.), University of Bordeaux 2, CHU Bordeaux, 33076 Bordeaux, France; Department of Endocrinology, Diabetes, and Metabolic Diseases (G.P.), CHU Rouen, 76031 Rouen, France; Ipsen Pharma (P.M., A.C.), 92100 Boulogne-Billancourt, France.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Caron
authors.forename: John S
authors.initials: JS
authors.lastname: Bevan
authors.forename: Stephan
authors.initials: S
authors.lastname: Petersenn
authors.forename: Daniel
authors.initials: D
authors.lastname: Flanagan
authors.forename: Antoine
authors.initials: A
authors.lastname: Tabarin
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Prévost
authors.forename: Pascal
authors.initials: P
authors.lastname: Maisonobe
authors.forename: Antoine
authors.initials: A
authors.lastname: Clermont
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000473:pathology; D000236:Adenoma / Q000188:drug therapy* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005782:Gels; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects*; D055815:Young Adult
chemical_list: D005782:Gels; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin