title: Impact of Previous Somatostatin Analogue Use on the Activity of Everolimus in Patients with Advanced Neuroendocrine Tumors: Analysis from the Phase III RADIANT-2 Trial.
abstract: OBJECTIVE
  The phase III placebo-controlled RADIANT-2 trial investigated the efficacy of everolimus plus octreotide long-acting repeatable (LAR) in patients with advanced neuroendocrine tumors (NET) associated with carcinoid syndrome. Here we report a secondary analysis based on the previous somatostatin analogue (SSA) exposure status of patients enrolled in RADIANT-2.
  
  
  METHODS
  Patients were randomly assigned to receive oral everolimus 10 mg/day plus octreotide LAR 30 mg intramuscularly (i.m.) or to receive matching placebo plus octreotide LAR 30 mg i.m. every 28 days. SSA treatment before study enrollment was permitted. Patient characteristics and progression-free survival (PFS) were analyzed by treatment arm and previous SSA exposure status.
  
  
  RESULTS
  Of the 429 patients enrolled in RADIANT-2, 339 were previously exposed to SSA (95% received octreotide); 173 of 339 patients were in the everolimus plus octreotide LAR arm. All patients had a protocol-specified history of secretory symptoms, but analysis by type showed that more patients who previously received SSA therapy had a history of flushing symptoms (77%), diarrhea (86%), or both (63%) compared with SSA-naive patients (62, 62, and 24%, respectively). Patients who received everolimus plus octreotide LAR had longer median PFS regardless of previous SSA exposure (with: PFS 14.3 months, 95% confidence interval, CI, 12.0-20.1; without: 25.2 months, 95% CI, 12.0-not reached) compared with patients who received placebo plus octreotide LAR (with: 11.1 months, 95% CI, 8.4-14.6; without: 13.6 months, 95% CI, 8.2-22.7).
  
  
  CONCLUSIONS
  Everolimus in combination with octreotide improves PFS in patients with advanced NET associated with carcinoid syndrome, regardless of previous SSA exposure.
authors.affiliation: Markey Cancer Center, University of Kentucky, Lexington, Ky., USA.
authors.forename: Lowell B
authors.initials: LB
authors.lastname: Anthony
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Pavel
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: Larry K
authors.initials: LK
authors.lastname: Kvols
authors.forename: Scott
authors.initials: S
authors.lastname: Segal
authors.forename: Dieter
authors.initials: D
authors.lastname: Hörsch
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Kjell
authors.initials: K
authors.lastname: Öberg
authors.forename: James C
authors.initials: JC
authors.lastname: Yao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000068338:Everolimus; D015282:Octreotide