title: Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study.
abstract: OBJECTIVE
  The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer.
  
  
  METHODS
  Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety.
  
  
  RESULTS
  Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW.
  
  
  CONCLUSIONS
  Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers.
authors.affiliation: Atsushi Ohtsu, National Cancer Center Hospital East, Kashiwa; Keisho Chin, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo; Kei Muro, Aichi Cancer Center Hospital, Nagoya, Japan; Jaffer A. Ajani, University of Texas MD Anderson Cancer Center, Houston, TX; Tarek Sahmoud, Heind Smith, Syed Rizvi, David Lebwohl, Novartis Pharmaceuticals, Florham Park, NJ; Yu-Xian Bai, Tumor Hospital of Harbin Medical University, Harbin; Hong-Ming Pan, Sir Run Run Shaw Hospital, Zhejiang; Lin Shen, Peking University Cancer Hospital, Beijing, People's Republic of China; Yung-Jue Bang, Seoul National University College of Medicine; Hyun-Cheol Chung, Yonsei Cancer Center, Yonsei University College of Medicine; Yeul Hong Kim, Korea University Anam Hospital, Seoul, South Korea; Kun-Huei Yeh, National Taiwan University Hospital, Taipei, Taiwan, Republic of China; David Ferry, New Cross Hospital, Wolverhampton, United Kingdom; Niall C. Tebbutt, Austin Health, Heidelberg, Australia; Salah-Eddin Al-Batran, Institute for Clinical Oncology Research, Krankenhaus Nordwest, UCT University Cancer Center, Frankfurt, Germany; Chiara Costantini, Novartis Pharma AG, Basel, Switzerland; Eric Van Cutsem, University Hospitals Leuven and KU Leuven, Leuven, Belgium.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.forename: Yu-Xian
authors.initials: YX
authors.lastname: Bai
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
authors.forename: Hyun-Cheol
authors.initials: HC
authors.lastname: Chung
authors.forename: Hong-Ming
authors.initials: HM
authors.lastname: Pan
authors.forename: Tarek
authors.initials: T
authors.lastname: Sahmoud
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
authors.forename: Kun-Huei
authors.initials: KH
authors.lastname: Yeh
authors.forename: Keisho
authors.initials: K
authors.lastname: Chin
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Yeul Hong
authors.initials: YH
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Ferry
authors.forename: Niall C
authors.initials: NC
authors.lastname: Tebbutt
authors.forename: Salah-Eddin
authors.initials: SE
authors.lastname: Al-Batran
authors.forename: Heind
authors.initials: H
authors.lastname: Smith
authors.forename: Chiara
authors.initials: C
authors.lastname: Costantini
authors.forename: Syed
authors.initials: S
authors.lastname: Rizvi
authors.forename: David
authors.initials: D
authors.lastname: Lebwohl
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D004311:Double-Blind Method; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D016016:Proportional Hazards Models; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus
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