PMID- 22119496
OWN - NLM
STAT- MEDLINE
DCOM- 20111229
LR  - 20220408
IS  - 1474-547X (Electronic)
IS  - 0140-6736 (Linking)
VI  - 378
IP  - 9808
DP  - 2011 Dec 10
TI  - Everolimus plus octreotide long-acting repeatable for the treatment of advanced 
      neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a 
      randomised, placebo-controlled, phase 3 study.
PG  - 2005-2012
LID - S0140-6736(11)61742-X [pii]
LID - 10.1016/S0140-6736(11)61742-X [doi]
AB  - BACKGROUND: Everolimus, an oral inhibitor of the mammalian target of rapamycin 
      (mTOR), has shown antitumour activity in patients with advanced pancreatic 
      neuroendocrine tumours. We aimed to assess the combination of everolimus plus 
      octreotide long-acting repeatable (LAR) in patients with low-grade or 
      intermediate-grade neuroendocrine tumours (carcinoid). METHODS: We did a 
      randomised, double-blind, placebo-controlled, phase 3 study comparing 10 mg per 
      day oral everolimus with placebo, both in conjunction with 30 mg intramuscular 
      octreotide LAR every 28 days. Randomisation was by interactive voice response 
      systems. Participants were aged 18 years or older, with low-grade or 
      intermediate-grade advanced (unresectable locally advanced or distant metastatic) 
      neuroendocrine tumours, and disease progression established by radiological 
      assessment within the past 12 months. Our primary endpoint was progression-free 
      survival. Adjusted for two interim analyses, the prespecified boundary at final 
      analysis was p</=0.0246. This study is registered at ClinicalTrials.gov, number 
      NCT00412061. FINDINGS: 429 individuals were randomly assigned to study groups; 
      357 participants discontinued study treatment and one was lost to follow-up. 
      Median progression-free survival by central review was 16.4 (95% CI 13.7-21.2) 
      months in the everolimus plus octreotide LAR group and 11.3 (8.4-14.6) months in 
      the placebo plus octreotide LAR group (hazard ratio 0.77, 95% CI 0.59-1.00; 
      one-sided log-rank test p=0.026). Drug-related adverse events (everolimus plus 
      octreotide LAR vs placebo plus octreotide LAR) were mostly grade 1 or 2, and 
      adverse events of all grades included stomatitis (62%vs 14%), rash (37%vs 12%), 
      fatigue (31%vs 23%), and diarrhoea (27%vs 16%). INTERPRETATION: Everolimus plus 
      octreotide LAR, compared with placebo plus octreotide LAR, improved 
      progression-free survival in patients with advanced neuroendocrine tumours 
      associated with carcinoid syndrome. FUNDING: Novartis Pharmaceuticals.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Pavel, Marianne E
AU  - Pavel ME
AD  - Charite-Universitatsmedizin Berlin/Campus Virchow Klinikum, Berlin, Germany.
FAU - Hainsworth, John D
AU  - Hainsworth JD
AD  - Sarah Cannon Research Institute, Nashville, TN, USA.
FAU - Baudin, Eric
AU  - Baudin E
AD  - Oncologie Endocrinienne et Medecine Nucleaire, Institut Gustave Roussy, 
      Villejuif, France.
FAU - Peeters, Marc
AU  - Peeters M
AD  - Department of Oncology, Antwerp University Hospital, Edegem, Belgium.
FAU - Horsch, Dieter
AU  - Horsch D
AD  - Klinik fur Innere Medizin, Gastroenterologie und Endokrinologie, Zentrum fur 
      Neuroendokrine Tumore, Zentralklinik Bad Berka GmbH, Bad Berka, Germany; Ochsner 
      Kenner Medical Center, Kenner, LA, USA.
FAU - Winkler, Robert E
AU  - Winkler RE
AD  - Novartis Oncology, Florham Park, NJ, USA.
FAU - Klimovsky, Judith
AU  - Klimovsky J
AD  - Novartis Oncology, Florham Park, NJ, USA.
FAU - Lebwohl, David
AU  - Lebwohl D
AD  - Novartis Oncology, Florham Park, NJ, USA.
FAU - Jehl, Valentine
AU  - Jehl V
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Wolin, Edward M
AU  - Wolin EM
AD  - Cedars Sinai Medical Center, Los Angeles, CA, USA.
FAU - Oberg, Kjell
AU  - Oberg K
AD  - Department of Endocrine Oncology, University Hospital, Uppsala, Sweden.
FAU - Van Cutsem, Eric
AU  - Van Cutsem E
AD  - University Hospital Gasthuisberg, Leuven, Belgium.
FAU - Yao, James C
AU  - Yao JC
AD  - University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic 
      address: jyao@mdanderson.org.
CN  - RADIANT-2 Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT00412061
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20111125
PL  - England
TA  - Lancet
JT  - Lancet (London, England)
JID - 2985213R
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - RWM8CCW8GP (Octreotide)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Lancet. 2011 Dec 10;378(9808):1978-80. PMID: 22119494
CIN - Nat Rev Endocrinol. 2012 Feb;8(2):66. PMID: 22158198
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents, Hormonal/*therapeutic use
MH  - Carcinoid Tumor/*drug therapy/pathology
MH  - Delayed-Action Preparations
MH  - Disease Progression
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Male
MH  - Malignant Carcinoid Syndrome/*drug therapy
MH  - Middle Aged
MH  - Octreotide/*therapeutic use
MH  - Sirolimus/*analogs & derivatives/therapeutic use
MH  - Young Adult
EDAT- 2011/11/29 06:00
MHDA- 2011/12/30 06:00
CRDT- 2011/11/29 06:00
PHST- 2011/11/29 06:00 [entrez]
PHST- 2011/11/29 06:00 [pubmed]
PHST- 2011/12/30 06:00 [medline]
AID - S0140-6736(11)61742-X [pii]
AID - 10.1016/S0140-6736(11)61742-X [doi]
PST - ppublish
SO  - Lancet. 2011 Dec 10;378(9808):2005-2012. doi: 10.1016/S0140-6736(11)61742-X. Epub 
      2011 Nov 25.