title: Coadministration of lanreotide Autogel and pegvisomant normalizes IGF1 levels and is well tolerated in patients with acromegaly partially controlled by somatostatin analogs alone.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of coadministered lanreotide Autogel (LA; 120  mg/month) and pegvisomant (40-120  mg/week) in acromegaly.
  
  
  METHODS
  This is a 28-week, multicenter, open-label, single-arm sequential study.
  
  
  METHODS
  Patients (n=92) biochemically uncontrolled, on somatostatin analogs (SSAs) or using pegvisomant monotherapy entered a 4-month run-in taking LA (120  mg/month). Patients uncontrolled after the run-in period (n=57) entered a 28-week coadministration period, receiving LA 120  mg/month plus pegvisomant (60  mg once weekly, adapted every 8 weeks based on IGF1 levels to 40-80  mg once weekly or 40 or 60  mg twice weekly).
  
  
  RESULTS
  In total, 33 (57.9%) patients had normalized IGF1 following coadministration (P<0.0001 versus 30% minimum clinically relevant); median pegvisomant dose in normalized patients was 60  mg/week. IGF1 normalized at any time during coadministration in 45 (78.9%) patients (P<0.0001) with median pegvisomant dose at 60  mg/week. Being nondiabetic (odds ratio (OR): 4.65) and older (OR, upper versus lower quartile: 3.40) showed increased likelihood of normalization. Symptom reduction was greatest for arthralgia (-0.6 ± 1.6) and soft tissue swelling (-0.6 ± 1.8). Five patients reported treatment-emergent adverse events causing treatment withdrawal: three serious (treatment related - thrombocytopenia, urticaria; not treatment related - abdominal pain/vomiting) and two nonserious (hepatotoxicity and cytolytic hepatitis, both elevating alanine aminotransferase to >5 × upper limit of normal with normalization after withdrawal).
  
  
  CONCLUSIONS
  In patients partially controlled by SSAs, LA (120  mg/month) plus pegvisomant normalized IGF1 in 57.9% of patients after 7 months, at a median effective pegvisomant dose of 60  mg/week, and 78.9% at any time. In these patients, results suggest a pegvisomant-sparing effect versus daily pegvisomant monotherapy.
authors.affiliation: Department of Internal Medicine, Erasmus University MC, 40 Dr Molewaterplein, 3015 GD Rotterdam, The Netherlands. a.vanderlelij@erasmusmc.nl
authors.forename: Aart-Jan
authors.initials: AJ
authors.lastname: van der Lely
authors.forename: Ignacio
authors.initials: I
authors.lastname: Bernabeu
authors.forename: Jan
authors.initials: J
authors.lastname: Cap
authors.forename: Philippe
authors.initials: P
authors.lastname: Caron
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Josef
authors.initials: J
authors.lastname: Marek
authors.forename: Sebastian
authors.initials: S
authors.lastname: Neggers
authors.forename: Pascal
authors.initials: P
authors.lastname: Birman
mesh_terms: D000172:Acromegaly / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D006728:Hormones / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D006728:Hormones; D010456:Peptides, Cyclic; C060347:lanreotide; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant