Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): A randomised, placebo-controlled, phase 3 study

J. C. Yao, Nicola Fazio, Simron Singh, Roberto Buzzoni, Carlo Carnaghi, Edward M. Wolin, Jiri Tomasek, Markus Raderer, Harald Lahner, M. Voi, Lida Bubuteishvili Pacaud, Nicolas Rouyrre, Carolin Sachs, Juan W. Valle, Gianfranco Delle Fave, Eric Van Cutsem, M. Tesselaar, Yasuhiro Shimada, Do Youn Oh, Jonathan R. StrosbergMatthew H. Kulke, Marianne Pavel

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish
Pages (from-to)968-977
Number of pages10
JournalThe Lancet
Volume387
Issue number10022
DOIs
Publication statusPublished - Mar 5 2016

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Neuroendocrine Tumors
Gastrointestinal Tract
Placebos
Lung
Therapeutics
Disease-Free Survival
Everolimus
Somatostatin
Radiology
Research Personnel
Safety
Survival
Population
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

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Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4) : A randomised, placebo-controlled, phase 3 study. / Yao, J. C.; Fazio, Nicola; Singh, Simron; Buzzoni, Roberto; Carnaghi, Carlo; Wolin, Edward M.; Tomasek, Jiri; Raderer, Markus; Lahner, Harald; Voi, M.; Pacaud, Lida Bubuteishvili; Rouyrre, Nicolas; Sachs, Carolin; Valle, Juan W.; Fave, Gianfranco Delle; Van Cutsem, Eric; Tesselaar, M.; Shimada, Yasuhiro; Oh, Do Youn; Strosberg, Jonathan R.; Kulke, Matthew H.; Pavel, Marianne.

In: The Lancet, Vol. 387, No. 10022, 05.03.2016, p. 968-977.

Research output: Contribution to journalArticle

Yao, JC, Fazio, N, Singh, S, Buzzoni, R, Carnaghi, C, Wolin, EM, Tomasek, J, Raderer, M, Lahner, H, Voi, M, Pacaud, LB, Rouyrre, N, Sachs, C, Valle, JW, Fave, GD, Van Cutsem, E, Tesselaar, M, Shimada, Y, Oh, DY, Strosberg, JR, Kulke, MH & Pavel, M 2016, 'Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): A randomised, placebo-controlled, phase 3 study', The Lancet, vol. 387, no. 10022, pp. 968-977. https://doi.org/10.1016/S0140-6736(15)00817-X
Yao, J. C. ; Fazio, Nicola ; Singh, Simron ; Buzzoni, Roberto ; Carnaghi, Carlo ; Wolin, Edward M. ; Tomasek, Jiri ; Raderer, Markus ; Lahner, Harald ; Voi, M. ; Pacaud, Lida Bubuteishvili ; Rouyrre, Nicolas ; Sachs, Carolin ; Valle, Juan W. ; Fave, Gianfranco Delle ; Van Cutsem, Eric ; Tesselaar, M. ; Shimada, Yasuhiro ; Oh, Do Youn ; Strosberg, Jonathan R. ; Kulke, Matthew H. ; Pavel, Marianne. / Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4) : A randomised, placebo-controlled, phase 3 study. In: The Lancet. 2016 ; Vol. 387, No. 10022. pp. 968-977.
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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

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