TY - JOUR
T1 - Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4)
T2 - A randomised, placebo-controlled, phase 3 study
AU - Yao, J. C.
AU - Fazio, Nicola
AU - Singh, Simron
AU - Buzzoni, Roberto
AU - Carnaghi, Carlo
AU - Wolin, Edward M.
AU - Tomasek, Jiri
AU - Raderer, Markus
AU - Lahner, Harald
AU - Voi, M.
AU - Pacaud, Lida Bubuteishvili
AU - Rouyrre, Nicolas
AU - Sachs, Carolin
AU - Valle, Juan W.
AU - Fave, Gianfranco Delle
AU - Van Cutsem, Eric
AU - Tesselaar, M.
AU - Shimada, Yasuhiro
AU - Oh, Do Youn
AU - Strosberg, Jonathan R.
AU - Kulke, Matthew H.
AU - Pavel, Marianne
PY - 2016/3/5
Y1 - 2016/3/5
N2 - Summary Background Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. We aimed to assess the efficacy and safety of everolimus compared with placebo in this patient population. Methods In the randomised, double-blind, placebo-controlled, phase 3 RADIANT-4 trial, adult patients (aged ≥18 years) with advanced, progressive, well-differentiated, non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide. Eligible patients were randomly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo, both with supportive care. Patients were stratified by tumour origin, performance status, and previous somatostatin analogue treatment. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival assessed by central radiology review, analysed by intention to treat. Overall survival was a key secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01524783. Findings Between April 3, 2012, and Aug 23, 2013, a total of 302 patients were enrolled, of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo. Median progression-free survival was 11·0 months (95% CI 9·2-13·3) in the everolimus group and 3·9 months (3·6-7·4) in the placebo group. Everolimus was associated with a 52% reduction in the estimated risk of progression or death (hazard ratio [HR] 0·48 [95% CI 0·35-0·67], p
AB - Summary Background Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. We aimed to assess the efficacy and safety of everolimus compared with placebo in this patient population. Methods In the randomised, double-blind, placebo-controlled, phase 3 RADIANT-4 trial, adult patients (aged ≥18 years) with advanced, progressive, well-differentiated, non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide. Eligible patients were randomly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo, both with supportive care. Patients were stratified by tumour origin, performance status, and previous somatostatin analogue treatment. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival assessed by central radiology review, analysed by intention to treat. Overall survival was a key secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01524783. Findings Between April 3, 2012, and Aug 23, 2013, a total of 302 patients were enrolled, of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo. Median progression-free survival was 11·0 months (95% CI 9·2-13·3) in the everolimus group and 3·9 months (3·6-7·4) in the placebo group. Everolimus was associated with a 52% reduction in the estimated risk of progression or death (hazard ratio [HR] 0·48 [95% CI 0·35-0·67], p
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U2 - 10.1016/S0140-6736(15)00817-X
DO - 10.1016/S0140-6736(15)00817-X
M3 - Article
VL - 387
SP - 968
EP - 977
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 10022
ER -