title: Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: an ITMO group study.
abstract: BACKGROUND
  Preclinical and clinical studies suggest synergistic activity between somatostatin analogues and mammalian target of rapamycin inhibitors. The activity and safety of everolimus was assessed in combination with octreotide long-acting repeatable (LAR) in patients with neuroendocrine tumors (NETs) of gastroenteropancreatic and lung origin.
  
  
  METHODS
  This was a phase 2, multicenter trial using a Simon's 2-stage minimax design. Treatment-naive patients with advanced well-differentiated NETs of gastroenteropancreatic tract and lung origin received everolimus 10 mg daily, in combination with octreotide LAR 30 mg every 28 days. The primary endpoint was objective response rate (ORR).
  
  
  RESULTS
  A total of 50 patients (median age, 60.5 years) were enrolled. Primary tumor sites were: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum and duodenum (2 patients), and unknown (14 patients). Thirteen patients (26%) had carcinoid syndrome. Treatment-related adverse events (AEs) were mostly grade 1 or 2; the only grade 4 AE was mucositis in 1 patient, whereas grade 3 AEs included skin rash in 1 case (2%), stomatitis in 4 cases (8%), and diarrhea in 11 cases (22%). The ORR was 18%; 2% of patients had a complete response (CR), 16% a partial response (PR) and 74% achieved stable disease (SD). All CRs and all PRs as well as 92% of SDs had a duration ≥ 6 months. The clinical benefit (CR+PR+SD) was 92%. At a median follow-up of 277 days, median time to progression and overall survival were not reached.
  
  
  CONCLUSIONS
  The everolimus-octreotide LAR combination was active and well tolerated in these previously treated patients with advanced NETs, suggesting a possible role as first-line treatment in patients with NET.
authors.affiliation: Institute of Oncology, Polyclinic Hospital, Monza, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
authors.forename: Laura
authors.initials: L
authors.lastname: Catena
authors.forename: Nicola
authors.initials: N
authors.lastname: Fazio
authors.forename: Sara
authors.initials: S
authors.lastname: Pusceddu
authors.forename: Pamela
authors.initials: P
authors.lastname: Biondani
authors.forename: Giusi
authors.initials: G
authors.lastname: Blanco
authors.forename: Sergio
authors.initials: S
authors.lastname: Ricci
authors.forename: Michele
authors.initials: M
authors.lastname: Aieta
authors.forename: Francesca
authors.initials: F
authors.lastname: Pucci
authors.forename: Monica
authors.initials: M
authors.lastname: Valente
authors.forename: Nadia
authors.initials: N
authors.lastname: Bianco
authors.forename: Chiara Maria
authors.initials: CM
authors.lastname: Mauri
authors.forename: Francesca
authors.initials: F
authors.lastname: Spada
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068338:Everolimus; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology; D015282:Octreotide / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000068338:Everolimus; D015282:Octreotide; D020123:Sirolimus
keywords: everolimus; neuroendocrine tumor; octreotide long-acting repeatable