Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: Analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study

Nicola Fazio, Dan Granberg, Ashley Grossman, Stephen Saletan, Judith Klimovsky, Ashok Panneerselvam, Edward M. Wolin

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Background: The incidence of neuroendocrine tumors (NETs) has increased approximately fivefold since the 1980s. A similar increase in the incidence of lung NETs has been reported, but therapy has not been optimized. Methods: This exploratory subanalysis evaluated the efficacy and safety of everolimus plus octreotide long-acting repeatable (LAR) in a cohort of patients with low- to intermediate-grade advanced lung NET from the phase 3, randomized, placebo-controlled RADIANT-2 (RAD001 in Advanced Neuroendocrine Tumors) study. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate, overall survival, change from baseline in biomarker levels, and safety outcomes. Results: Patients were randomly assigned to everolimus plus octreotide LAR (n = 33) or placebo plus octreotide LAR (n = 11). Median PFS was 13.63 months in the everolimus plus octreotide LAR arm compared with 5.59 months in the placebo plus octreotide LAR arm (relative risk for progression: HR, 0.72; 95% CI, 0.31-1.68; P = .228). More patients receiving everolimus plus octreotide LAR (67%) experienced minor tumor shrinkage (not partial response as per RECIST [Response Evaluation Criteria in Solid Tumors]) than those receiving placebo plus octreotide LAR (27%). Most frequently reported adverse events (AEs) included stomatitis, rash, diarrhea, and asthenia. This was consistent with the overall RADIANT-2 trial and the safety profile of everolimus. Conclusions: This exploratory subgroup analysis of the RADIANT-2 trial indicates that in patients with advanced lung NET, the addition of everolimus to octreotide LAR improves median PFS by 2.4-fold compared with placebo plus octreotide LAR. These clinically significant observations support the continued evaluation of everolimus treatment regimens in this patient population.

Original languageEnglish (US)
Pages (from-to)955-962
Number of pages8
JournalChest
Volume143
Issue number4
DOIs
StatePublished - Apr 2013
Externally publishedYes

Fingerprint

Octreotide
Neuroendocrine Tumors
Placebos
Lung
Disease-Free Survival
Safety
Everolimus
Asthenia
Stomatitis
Incidence
Exanthema
Diarrhea
Survival Rate
Biomarkers

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors : Analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study. / Fazio, Nicola; Granberg, Dan; Grossman, Ashley; Saletan, Stephen; Klimovsky, Judith; Panneerselvam, Ashok; Wolin, Edward M.

In: Chest, Vol. 143, No. 4, 04.2013, p. 955-962.

Research output: Contribution to journalArticle

Fazio, Nicola ; Granberg, Dan ; Grossman, Ashley ; Saletan, Stephen ; Klimovsky, Judith ; Panneerselvam, Ashok ; Wolin, Edward M. / Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors : Analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study. In: Chest. 2013 ; Vol. 143, No. 4. pp. 955-962.
@article{94391ee39ea447b79dce9433459d077e,
title = "Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: Analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study",
abstract = "Background: The incidence of neuroendocrine tumors (NETs) has increased approximately fivefold since the 1980s. A similar increase in the incidence of lung NETs has been reported, but therapy has not been optimized. Methods: This exploratory subanalysis evaluated the efficacy and safety of everolimus plus octreotide long-acting repeatable (LAR) in a cohort of patients with low- to intermediate-grade advanced lung NET from the phase 3, randomized, placebo-controlled RADIANT-2 (RAD001 in Advanced Neuroendocrine Tumors) study. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate, overall survival, change from baseline in biomarker levels, and safety outcomes. Results: Patients were randomly assigned to everolimus plus octreotide LAR (n = 33) or placebo plus octreotide LAR (n = 11). Median PFS was 13.63 months in the everolimus plus octreotide LAR arm compared with 5.59 months in the placebo plus octreotide LAR arm (relative risk for progression: HR, 0.72; 95{\%} CI, 0.31-1.68; P = .228). More patients receiving everolimus plus octreotide LAR (67{\%}) experienced minor tumor shrinkage (not partial response as per RECIST [Response Evaluation Criteria in Solid Tumors]) than those receiving placebo plus octreotide LAR (27{\%}). Most frequently reported adverse events (AEs) included stomatitis, rash, diarrhea, and asthenia. This was consistent with the overall RADIANT-2 trial and the safety profile of everolimus. Conclusions: This exploratory subgroup analysis of the RADIANT-2 trial indicates that in patients with advanced lung NET, the addition of everolimus to octreotide LAR improves median PFS by 2.4-fold compared with placebo plus octreotide LAR. These clinically significant observations support the continued evaluation of everolimus treatment regimens in this patient population.",
author = "Nicola Fazio and Dan Granberg and Ashley Grossman and Stephen Saletan and Judith Klimovsky and Ashok Panneerselvam and Wolin, {Edward M.}",
year = "2013",
month = "4",
doi = "10.1378/chest.12-1108",
language = "English (US)",
volume = "143",
pages = "955--962",
journal = "Chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "4",

}

TY - JOUR

T1 - Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors

T2 - Analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study

AU - Fazio, Nicola

AU - Granberg, Dan

AU - Grossman, Ashley

AU - Saletan, Stephen

AU - Klimovsky, Judith

AU - Panneerselvam, Ashok

AU - Wolin, Edward M.

PY - 2013/4

Y1 - 2013/4

N2 - Background: The incidence of neuroendocrine tumors (NETs) has increased approximately fivefold since the 1980s. A similar increase in the incidence of lung NETs has been reported, but therapy has not been optimized. Methods: This exploratory subanalysis evaluated the efficacy and safety of everolimus plus octreotide long-acting repeatable (LAR) in a cohort of patients with low- to intermediate-grade advanced lung NET from the phase 3, randomized, placebo-controlled RADIANT-2 (RAD001 in Advanced Neuroendocrine Tumors) study. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate, overall survival, change from baseline in biomarker levels, and safety outcomes. Results: Patients were randomly assigned to everolimus plus octreotide LAR (n = 33) or placebo plus octreotide LAR (n = 11). Median PFS was 13.63 months in the everolimus plus octreotide LAR arm compared with 5.59 months in the placebo plus octreotide LAR arm (relative risk for progression: HR, 0.72; 95% CI, 0.31-1.68; P = .228). More patients receiving everolimus plus octreotide LAR (67%) experienced minor tumor shrinkage (not partial response as per RECIST [Response Evaluation Criteria in Solid Tumors]) than those receiving placebo plus octreotide LAR (27%). Most frequently reported adverse events (AEs) included stomatitis, rash, diarrhea, and asthenia. This was consistent with the overall RADIANT-2 trial and the safety profile of everolimus. Conclusions: This exploratory subgroup analysis of the RADIANT-2 trial indicates that in patients with advanced lung NET, the addition of everolimus to octreotide LAR improves median PFS by 2.4-fold compared with placebo plus octreotide LAR. These clinically significant observations support the continued evaluation of everolimus treatment regimens in this patient population.

AB - Background: The incidence of neuroendocrine tumors (NETs) has increased approximately fivefold since the 1980s. A similar increase in the incidence of lung NETs has been reported, but therapy has not been optimized. Methods: This exploratory subanalysis evaluated the efficacy and safety of everolimus plus octreotide long-acting repeatable (LAR) in a cohort of patients with low- to intermediate-grade advanced lung NET from the phase 3, randomized, placebo-controlled RADIANT-2 (RAD001 in Advanced Neuroendocrine Tumors) study. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate, overall survival, change from baseline in biomarker levels, and safety outcomes. Results: Patients were randomly assigned to everolimus plus octreotide LAR (n = 33) or placebo plus octreotide LAR (n = 11). Median PFS was 13.63 months in the everolimus plus octreotide LAR arm compared with 5.59 months in the placebo plus octreotide LAR arm (relative risk for progression: HR, 0.72; 95% CI, 0.31-1.68; P = .228). More patients receiving everolimus plus octreotide LAR (67%) experienced minor tumor shrinkage (not partial response as per RECIST [Response Evaluation Criteria in Solid Tumors]) than those receiving placebo plus octreotide LAR (27%). Most frequently reported adverse events (AEs) included stomatitis, rash, diarrhea, and asthenia. This was consistent with the overall RADIANT-2 trial and the safety profile of everolimus. Conclusions: This exploratory subgroup analysis of the RADIANT-2 trial indicates that in patients with advanced lung NET, the addition of everolimus to octreotide LAR improves median PFS by 2.4-fold compared with placebo plus octreotide LAR. These clinically significant observations support the continued evaluation of everolimus treatment regimens in this patient population.

UR - http://www.scopus.com/inward/record.url?scp=84875989281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875989281&partnerID=8YFLogxK

U2 - 10.1378/chest.12-1108

DO - 10.1378/chest.12-1108

M3 - Article

C2 - 23187897

AN - SCOPUS:84875989281

VL - 143

SP - 955

EP - 962

JO - Chest

JF - Chest

SN - 0012-3692

IS - 4

ER -