title: Everolimus for advanced pancreatic neuroendocrine tumours: a subgroup analysis evaluating Japanese patients in the RADIANT-3 trial.
abstract: OBJECTIVE
  Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65% risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study.
  
  
  METHODS
  Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions.
  
  
  RESULTS
  Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95% confidence interval, 8.31-not available) with everolimus vs 2.83 months (95% confidence interval, 2.46-8.34) with placebo, resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95% confidence interval, 0.08-0.48; P< 0.001). Adverse drug reactions occurred in all 23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17; 74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10; 44%) and pneumonitis (n = 10; 44%).
  
  
  CONCLUSIONS
  These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours.
authors.affiliation: Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan. itopapa@intmed3.med.kyushu-u.ac.jp
authors.forename: Tetsuhide
authors.initials: T
authors.lastname: Ito
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Hisato
authors.initials: H
authors.lastname: Igarashi
authors.forename: Chigusa
authors.initials: C
authors.lastname: Morizane
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tajima
authors.forename: Akio
authors.initials: A
authors.lastname: Kasuga
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Fujita
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017326:Clinical Trials, Phase III as Topic; D004311:Double-Blind Method; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000401:mortality; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015996:Survival Rate; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus