Everolimus for the treatment of advanced pancreatic neuroendocrine tumors: Overall survival and circulating biomarkers from the randomized, Phase III RADIANT-3 study

James C. Yao, Marianne Pavel, Catherine Lombard-Bohas, Eric Van Cutsem, Maurizio Voi, Ulrike Brandt, Wei He, David Chen, Jaume Capdevila, Elisabeth G E De Vries, Paola Tomassetti, Timothy James Hobday, Rodney Pommier, Kjell Öberg

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors (NET) compared with placebo in the RADIANT-3 study. Here, we present the final overall survival (OS) data and data on the impact of biomarkers on OS from the RADIANT-3 study. Methods Patients with advanced, progressive, low- or intermediate-grade pancreatic NET were randomly assigned to everolimus 10 mg/day (n = 207) or placebo (n = 203). Crossover from placebo to openlabel everolimus was allowed on disease progression. Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator's discretion (extension phase). OS analysis was performed using a stratified log-rank test in the intentto- treat population. The baseline levels of chromogranin A, neuron-specific enolase, and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored. Results Of 410 patients who were enrolled between July 2007 and March 2014, 225 received open-label everolimus, including 172 patients (85%) randomly assigned initially to the placebo arm. Median OS was 44.0 months (95% CI, 35.6 to 51.8 months) for those randomly assigned to everolimus and 37.7 months (95% CI, 29.1 to 45.8 months) for those randomly assigned to placebo (hazard ratio, 0.94; 95% CI, 0.73 to 1.20; P = .30). Elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS. The most common adverse events included stomatitis, rash, and diarrhea. Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced, progressive pancreatic NET, the longest OS reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of patients likely confounded the OS results.

Original languageEnglish (US)
Pages (from-to)3906-3913
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number32
DOIs
StatePublished - Nov 10 2016

Fingerprint

Neuroendocrine Tumors
Biomarkers
Survival
Placebos
Chromogranin A
Therapeutics
Phosphopyruvate Hydratase
Survival Analysis
Disease-Free Survival
Vascular Endothelial Growth Factor Receptor-1
Everolimus
Stomatitis
Exanthema
Population
Disease Progression
Diarrhea
Intercellular Signaling Peptides and Proteins
Research Personnel

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Everolimus for the treatment of advanced pancreatic neuroendocrine tumors : Overall survival and circulating biomarkers from the randomized, Phase III RADIANT-3 study. / Yao, James C.; Pavel, Marianne; Lombard-Bohas, Catherine; Van Cutsem, Eric; Voi, Maurizio; Brandt, Ulrike; He, Wei; Chen, David; Capdevila, Jaume; De Vries, Elisabeth G E; Tomassetti, Paola; Hobday, Timothy James; Pommier, Rodney; Öberg, Kjell.

In: Journal of Clinical Oncology, Vol. 34, No. 32, 10.11.2016, p. 3906-3913.

Research output: Contribution to journalArticle

Yao, JC, Pavel, M, Lombard-Bohas, C, Van Cutsem, E, Voi, M, Brandt, U, He, W, Chen, D, Capdevila, J, De Vries, EGE, Tomassetti, P, Hobday, TJ, Pommier, R & Öberg, K 2016, 'Everolimus for the treatment of advanced pancreatic neuroendocrine tumors: Overall survival and circulating biomarkers from the randomized, Phase III RADIANT-3 study', Journal of Clinical Oncology, vol. 34, no. 32, pp. 3906-3913. https://doi.org/10.1200/JCO.2016.68.0702
Yao, James C. ; Pavel, Marianne ; Lombard-Bohas, Catherine ; Van Cutsem, Eric ; Voi, Maurizio ; Brandt, Ulrike ; He, Wei ; Chen, David ; Capdevila, Jaume ; De Vries, Elisabeth G E ; Tomassetti, Paola ; Hobday, Timothy James ; Pommier, Rodney ; Öberg, Kjell. / Everolimus for the treatment of advanced pancreatic neuroendocrine tumors : Overall survival and circulating biomarkers from the randomized, Phase III RADIANT-3 study. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 32. pp. 3906-3913.
@article{4313dc98f1e547f7bce718ce40412c73,
title = "Everolimus for the treatment of advanced pancreatic neuroendocrine tumors: Overall survival and circulating biomarkers from the randomized, Phase III RADIANT-3 study",
abstract = "Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors (NET) compared with placebo in the RADIANT-3 study. Here, we present the final overall survival (OS) data and data on the impact of biomarkers on OS from the RADIANT-3 study. Methods Patients with advanced, progressive, low- or intermediate-grade pancreatic NET were randomly assigned to everolimus 10 mg/day (n = 207) or placebo (n = 203). Crossover from placebo to openlabel everolimus was allowed on disease progression. Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator's discretion (extension phase). OS analysis was performed using a stratified log-rank test in the intentto- treat population. The baseline levels of chromogranin A, neuron-specific enolase, and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored. Results Of 410 patients who were enrolled between July 2007 and March 2014, 225 received open-label everolimus, including 172 patients (85{\%}) randomly assigned initially to the placebo arm. Median OS was 44.0 months (95{\%} CI, 35.6 to 51.8 months) for those randomly assigned to everolimus and 37.7 months (95{\%} CI, 29.1 to 45.8 months) for those randomly assigned to placebo (hazard ratio, 0.94; 95{\%} CI, 0.73 to 1.20; P = .30). Elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS. The most common adverse events included stomatitis, rash, and diarrhea. Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced, progressive pancreatic NET, the longest OS reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of patients likely confounded the OS results.",
author = "Yao, {James C.} and Marianne Pavel and Catherine Lombard-Bohas and {Van Cutsem}, Eric and Maurizio Voi and Ulrike Brandt and Wei He and David Chen and Jaume Capdevila and {De Vries}, {Elisabeth G E} and Paola Tomassetti and Hobday, {Timothy James} and Rodney Pommier and Kjell {\"O}berg",
year = "2016",
month = "11",
day = "10",
doi = "10.1200/JCO.2016.68.0702",
language = "English (US)",
volume = "34",
pages = "3906--3913",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "32",

}

TY - JOUR

T1 - Everolimus for the treatment of advanced pancreatic neuroendocrine tumors

T2 - Overall survival and circulating biomarkers from the randomized, Phase III RADIANT-3 study

AU - Yao, James C.

AU - Pavel, Marianne

AU - Lombard-Bohas, Catherine

AU - Van Cutsem, Eric

AU - Voi, Maurizio

AU - Brandt, Ulrike

AU - He, Wei

AU - Chen, David

AU - Capdevila, Jaume

AU - De Vries, Elisabeth G E

AU - Tomassetti, Paola

AU - Hobday, Timothy James

AU - Pommier, Rodney

AU - Öberg, Kjell

PY - 2016/11/10

Y1 - 2016/11/10

N2 - Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors (NET) compared with placebo in the RADIANT-3 study. Here, we present the final overall survival (OS) data and data on the impact of biomarkers on OS from the RADIANT-3 study. Methods Patients with advanced, progressive, low- or intermediate-grade pancreatic NET were randomly assigned to everolimus 10 mg/day (n = 207) or placebo (n = 203). Crossover from placebo to openlabel everolimus was allowed on disease progression. Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator's discretion (extension phase). OS analysis was performed using a stratified log-rank test in the intentto- treat population. The baseline levels of chromogranin A, neuron-specific enolase, and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored. Results Of 410 patients who were enrolled between July 2007 and March 2014, 225 received open-label everolimus, including 172 patients (85%) randomly assigned initially to the placebo arm. Median OS was 44.0 months (95% CI, 35.6 to 51.8 months) for those randomly assigned to everolimus and 37.7 months (95% CI, 29.1 to 45.8 months) for those randomly assigned to placebo (hazard ratio, 0.94; 95% CI, 0.73 to 1.20; P = .30). Elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS. The most common adverse events included stomatitis, rash, and diarrhea. Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced, progressive pancreatic NET, the longest OS reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of patients likely confounded the OS results.

AB - Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors (NET) compared with placebo in the RADIANT-3 study. Here, we present the final overall survival (OS) data and data on the impact of biomarkers on OS from the RADIANT-3 study. Methods Patients with advanced, progressive, low- or intermediate-grade pancreatic NET were randomly assigned to everolimus 10 mg/day (n = 207) or placebo (n = 203). Crossover from placebo to openlabel everolimus was allowed on disease progression. Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator's discretion (extension phase). OS analysis was performed using a stratified log-rank test in the intentto- treat population. The baseline levels of chromogranin A, neuron-specific enolase, and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored. Results Of 410 patients who were enrolled between July 2007 and March 2014, 225 received open-label everolimus, including 172 patients (85%) randomly assigned initially to the placebo arm. Median OS was 44.0 months (95% CI, 35.6 to 51.8 months) for those randomly assigned to everolimus and 37.7 months (95% CI, 29.1 to 45.8 months) for those randomly assigned to placebo (hazard ratio, 0.94; 95% CI, 0.73 to 1.20; P = .30). Elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS. The most common adverse events included stomatitis, rash, and diarrhea. Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced, progressive pancreatic NET, the longest OS reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of patients likely confounded the OS results.

UR - http://www.scopus.com/inward/record.url?scp=84995529374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84995529374&partnerID=8YFLogxK

U2 - 10.1200/JCO.2016.68.0702

DO - 10.1200/JCO.2016.68.0702

M3 - Article

C2 - 27621394

AN - SCOPUS:84995529374

VL - 34

SP - 3906

EP - 3913

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 32

ER -