PMID- 24043745
OWN - NLM
STAT- MEDLINE
DCOM- 20131231
LR  - 20220408
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 31
IP  - 31
DP  - 2013 Nov 1
TI  - Everolimus for previously treated advanced gastric cancer: results of the 
      randomized, double-blind, phase III GRANITE-1 study.
PG  - 3935-43
LID - 10.1200/JCO.2012.48.3552 [doi]
AB  - PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.
FAU - Ohtsu, Atsushi
AU  - Ohtsu A
AD  - 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.
FAU - Ajani, Jaffer A
AU  - Ajani JA
FAU - Bai, Yu-Xian
AU  - Bai YX
FAU - Bang, Yung-Jue
AU  - Bang YJ
FAU - Chung, Hyun-Cheol
AU  - Chung HC
FAU - Pan, Hong-Ming
AU  - Pan HM
FAU - Sahmoud, Tarek
AU  - Sahmoud T
FAU - Shen, Lin
AU  - Shen L
FAU - Yeh, Kun-Huei
AU  - Yeh KH
FAU - Chin, Keisho
AU  - Chin K
FAU - Muro, Kei
AU  - Muro K
FAU - Kim, Yeul Hong
AU  - Kim YH
FAU - Ferry, David
AU  - Ferry D
FAU - Tebbutt, Niall C
AU  - Tebbutt NC
FAU - Al-Batran, Salah-Eddin
AU  - Al-Batran SE
FAU - Smith, Heind
AU  - Smith H
FAU - Costantini, Chiara
AU  - Costantini C
FAU - Rizvi, Syed
AU  - Rizvi S
FAU - Lebwohl, David
AU  - Lebwohl D
FAU - Van Cutsem, Eric
AU  - Van Cutsem E
LA  - eng
SI  - ClinicalTrials.gov/NCT00879333
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130916
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenocarcinoma/*drug therapy/mortality
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Disease-Free Survival
MH  - Double-Blind Method
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Proportional Hazards Models
MH  - Sirolimus/*analogs & derivatives/therapeutic use
MH  - Stomach Neoplasms/*drug therapy/mortality
MH  - Young Adult
PMC - PMC5950503
COIS- Authors' disclosures of potential conflicts of interest and author contributions 
      are found at the end of this article.
EDAT- 2013/09/18 06:00
MHDA- 2014/01/01 06:00
PMCR- 2013/09/16
CRDT- 2013/09/18 06:00
PHST- 2013/09/18 06:00 [entrez]
PHST- 2013/09/18 06:00 [pubmed]
PHST- 2014/01/01 06:00 [medline]
PHST- 2013/09/16 00:00 [pmc-release]
AID - JCO.2012.48.3552 [pii]
AID - 83552 [pii]
AID - 10.1200/JCO.2012.48.3552 [doi]
PST - ppublish
SO  - J Clin Oncol. 2013 Nov 1;31(31):3935-43. doi: 10.1200/JCO.2012.48.3552. Epub 2013 
      Sep 16.