title: Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study.
abstract: BACKGROUND
  The incidence of neuroendocrine tumors (NETs) has increased approximately fivefold since the 1980s. A similar increase in the incidence of lung NETs has been reported, but therapy has not been optimized.
  
  
  METHODS
  This exploratory subanalysis evaluated the efficacy and safety of everolimus plus octreotide long-acting repeatable (LAR) in a cohort of patients with low- to intermediate-grade advanced lung NET from the phase 3, randomized, placebo-controlled RADIANT-2 (RAD001 in Advanced Neuroendocrine Tumors) study. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate, overall survival, change from baseline in biomarker levels, and safety outcomes.
  
  
  RESULTS
  Patients were randomly assigned to everolimus plus octreotide LAR (n 5 33) or placebo plus octreotide LAR (n 5 11). Median PFS was 13.63 months in the everolimus plus octreotide LAR arm compared with 5.59 months in the placebo plus octreotide LAR arm (relative risk for progression: HR, 0.72; 95% CI, 0.31–1.68; P 5 .228). More patients receiving everolimus plus octreotide LAR (67%) experienced minor tumor shrinkage (not partial response as per RECIST [Response Evaluation Criteria in Solid Tumors]) than those receiving placebo plus octreotide LAR (27%). Most frequently reported adverse events (AEs) included stomatitis, rash, diarrhea, and asthenia. This was consistent with the overall RADIANT-2 trial and the safety profile of everolimus.
  
  
  CONCLUSIONS
  This exploratory subgroup analysis of the RADIANT-2 trial indicates that in patients with advanced lung NET, the addition of everolimus to octreotide LAR improves median PFS by 2.4-fold compared with placebo plus octreotide LAR. These clinically significant observations support the continued evaluation of everolimus treatment regimens in this patient population.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT00412061
authors.affiliation: European Institute of Oncology, Milan, Italy. Electronic address: nicola.fazio@ieo.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fazio
authors.affiliation: Departments of Medical Sciences and Endocrine Oncology, Uppsala University, Uppsala, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Granberg
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital University of Oxford, Oxford, England.
authors.forename: Ashley
authors.initials: A
authors.lastname: Grossman
authors.affiliation: Novartis Pharmaceuticals Corp, Florham Park, NJ.
authors.forename: Stephen
authors.initials: S
authors.lastname: Saletan
authors.affiliation: Novartis Pharmaceuticals Corp, Florham Park, NJ.
authors.forename: Judith
authors.initials: J
authors.lastname: Klimovsky
authors.affiliation: Novartis Pharmaceuticals Corp, Florham Park, NJ.
authors.forename: Ashok
authors.initials: A
authors.lastname: Panneerselvam
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Wolin
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015282:Octreotide / Q000009:adverse effects / Q000627:therapeutic use*; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000068338:Everolimus; D015282:Octreotide; D020123:Sirolimus