TY - JOUR
T1 - Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2)
T2 - A randomised, placebo-controlled, phase 3 study
AU - Pavel, Marianne E.
AU - Hainsworth, John D.
AU - Baudin, Eric
AU - Peeters, Marc
AU - Hörsch, Dieter
AU - Winkler, Robert E.
AU - Klimovsky, Judith
AU - Lebwohl, David
AU - Jehl, Valentine
AU - Wolin, Edward M.
AU - Öberg, Kjell
AU - Van Cutsem, Eric
AU - Yao, James C.
N1 - Funding Information:
MEP has served as a consultant and has received honoraria and research funding from Novartis. EB has received honoraria or research funding from Novartis. MP has received research funding and is on the speaker's bureau for Novartis. DH is a consultant to and has received honoraria and research funding from Novartis. REW, JK, DL, and VJ are employees of and own shares in Novartis. EMW is a consultant to Novartis. KO serves on advisory boards of and receives honoraria from Novartis, Pfizer, and Ipsen. EVC has received research funding from Novartis. JCY is a consultant to Novartis and has received research funding from Novartis. JDH declares no conflicts of interest.
PY - 2011/12/10
Y1 - 2011/12/10
N2 - 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). 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. 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). Everolimus plus octreotide LAR, compared with placebo plus octreotide LAR, improved progression-free survival in patients with advanced neuroendocrine tumours associated with carcinoid syndrome. Novartis Pharmaceuticals.
AB - 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). 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. 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). Everolimus plus octreotide LAR, compared with placebo plus octreotide LAR, improved progression-free survival in patients with advanced neuroendocrine tumours associated with carcinoid syndrome. Novartis Pharmaceuticals.
UR - http://www.scopus.com/inward/record.url?scp=83255167036&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(11)61742-X
DO - 10.1016/S0140-6736(11)61742-X
M3 - Article
C2 - 22119496
AN - SCOPUS:83255167036
SN - 0140-6736
VL - 378
SP - 2005
EP - 2012
JO - The Lancet
JF - The Lancet
IS - 9808
ER -