title: Impact of prior chemotherapy use on the efficacy of everolimus in patients with advanced pancreatic neuroendocrine tumors: a subgroup analysis of the phase III RADIANT-3 trial.
abstract: OBJECTIVE
  The aim of this study was to evaluate efficacy and safety of everolimus in patients with pancreatic neuroendocrine tumors (pNET) by prior chemotherapy use in the RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3).
  
  
  METHODS
  Patients with advanced, progressive, low- or intermediate-grade pNET were prospectively stratified by prior chemotherapy use and World Health Organization performance status and were randomly assigned (1:1) to everolimus 10 mg/d (n = 207) or placebo (n = 203).
  
  
  RESULTS
  Of the 410 patients, 204 (50%) were naive to chemotherapy (chemonaive). Baseline characteristics were similar for patients with or without prior chemotherapy. Everolimus significantly prolonged median progression-free survival regardless of prior chemotherapy use (prior chemotherapy: 11.0 vs 3.2 months; hazard ratio, 0.34; 95% confidence interval, 0.25-0.48; P < 0.0001) (chemonaive: 11.4 vs 5.4 months; hazard ratio, 0.42; 95% confidence interval, 0.29-0.60; P < 0.0001). Stable disease was the best overall response in 73% of everolimus-treated patients (151/207). The most common drug-related adverse events included stomatitis (60%-69%), rash (47%-50%), and diarrhea (34%).
  
  
  CONCLUSIONS
  As more treatment options become available, it is important to consider the goals of treatment and to identify patients who would potentially benefit from a specific therapy. Findings from this planned subgroup analysis suggest the potential for first-line use of everolimus in patients with advanced pNET.
authors.affiliation: From the *Department of Medical Oncology, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; †Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; ‡Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN; §Digestive Oncology, University Hospitals Gasthuisberg/Leuven, Leuven, Belgium; ∥Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA; ¶Department of Oncology Biometrics and Data, and #Department of Oncology, Novartis Pharmaceuticals Corporation, East Hanover, NJ; **Department of Medical Oncology, The Ohio State University, Columbus, OH; ††Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain; and ‡‡Division of Surgical Oncology, Oregon Health & Science University, Portland, OR.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lombard-Bohas
authors.forename: James C
authors.initials: JC
authors.lastname: Yao
authors.forename: Timothy
authors.initials: T
authors.lastname: Hobday
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Edward M
authors.initials: EM
authors.lastname: Wolin
authors.forename: Ashok
authors.initials: A
authors.lastname: Panneerselvam
authors.forename: Sotirios
authors.initials: S
authors.lastname: Stergiopoulos
authors.forename: Manisha H
authors.initials: MH
authors.lastname: Shah
authors.forename: Jaume
authors.initials: J
authors.lastname: Capdevila
authors.forename: Rodney
authors.initials: R
authors.lastname: Pommier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D000068338:Everolimus / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018579:Patient Selection; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus