Impact of prior therapies on everolimus activity: An exploratory analysis of RADIANT-4

Roberto Buzzoni, Carlo Carnaghi, Jonathan Strosberg, Nicola Fazio, Simron Singh, Fabian Herbst, Antonia Ridolfi, Marianne E. Pavel, Edward M. Wolin, Juan W. Valle, Do Youn Oh, James C. Yao, Rodney Pommier

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Recently, everolimus was shown to improve median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of lung or gastrointestinal (GI) tract compared with placebo (HR, 0.48; 95% CI, 0.35–0.67; P<0.00001) in the Phase III, RADIANT-4 study. This post hoc analysis evaluates the impact of prior therapies (somatostatin analogs [SSA], chemotherapy, and radiotherapy) on everolimus activity. Trial registration: ClinicalTrials.gov identifier: NCT01524783. Patients and methods: Patients were randomized (2:1) to everolimus 10 mg/day or placebo, both with best supportive care. Subgroups of patients who received prior SSA, chemotherapy, or radiotherapy (including peptide receptor radionuclide therapy) were analyzed and reported. Results: A total of 302 patients were enrolled, of whom, 163 (54%) had any prior SSA use (mostly for tumor control), 77 (25%) received chemotherapy, and 63 (21%) were previously exposed to radiotherapy. Patients who received everolimus had longer median PFS compared with placebo, regardless of previous SSA (with SSA: 11.1 vs 4.5 months [HR, 0.56 {95% CI, 0.37–0.85}]; without SSA: 9.5 vs 3.7 months [0.57 {0.36–0.89}]), chemotherapy (with chemotherapy: 9.2 vs 2.1 months [0.35 {0.19–0.64}]; without chemotherapy: 11.2 vs 5.4 months [0.60 {0.42–0.86}]), or radiotherapy (with radiotherapy: 9.2 vs 3.0 months [0.47 {0.24–0.94}]; without radiotherapy: 11 vs 5.1 months [0.59 {0.42–0.83}]) exposure. The most frequent drug-related adverse events included stomatitis (59%–65%), fatigue (27%–35%), and diarrhea (24%–34%) among the subgroups. Conclusion: These results suggest that everolimus improves PFS in patients with advanced, progressive lung or GI NET, regardless of prior therapies. Safety findings were consistent with the known safety profile of everolimus in NET.

Original languageEnglish (US)
Pages (from-to)5013-5030
Number of pages18
JournalOncoTargets and Therapy
Volume10
DOIs
StatePublished - Oct 16 2017

Fingerprint

Peptide Receptors
Somatostatin
Radioisotopes
Drug Therapy
Neuroendocrine Tumors
Disease-Free Survival
Placebos
Therapeutics
Safety
Lung
Stomatitis
Everolimus
Drug-Related Side Effects and Adverse Reactions
Fatigue
Gastrointestinal Tract
Diarrhea
Neoplasms

Keywords

  • Chemotherapy
  • Neuroendocrine tumors
  • Progression-free survival
  • PRRT
  • Somatostatin analogs

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

Cite this

Buzzoni, R., Carnaghi, C., Strosberg, J., Fazio, N., Singh, S., Herbst, F., ... Pommier, R. (2017). Impact of prior therapies on everolimus activity: An exploratory analysis of RADIANT-4. OncoTargets and Therapy, 10, 5013-5030. https://doi.org/10.2147/OTT.S142087

Impact of prior therapies on everolimus activity : An exploratory analysis of RADIANT-4. / Buzzoni, Roberto; Carnaghi, Carlo; Strosberg, Jonathan; Fazio, Nicola; Singh, Simron; Herbst, Fabian; Ridolfi, Antonia; Pavel, Marianne E.; Wolin, Edward M.; Valle, Juan W.; Oh, Do Youn; Yao, James C.; Pommier, Rodney.

In: OncoTargets and Therapy, Vol. 10, 16.10.2017, p. 5013-5030.

Research output: Contribution to journalArticle

Buzzoni, R, Carnaghi, C, Strosberg, J, Fazio, N, Singh, S, Herbst, F, Ridolfi, A, Pavel, ME, Wolin, EM, Valle, JW, Oh, DY, Yao, JC & Pommier, R 2017, 'Impact of prior therapies on everolimus activity: An exploratory analysis of RADIANT-4', OncoTargets and Therapy, vol. 10, pp. 5013-5030. https://doi.org/10.2147/OTT.S142087
Buzzoni R, Carnaghi C, Strosberg J, Fazio N, Singh S, Herbst F et al. Impact of prior therapies on everolimus activity: An exploratory analysis of RADIANT-4. OncoTargets and Therapy. 2017 Oct 16;10:5013-5030. https://doi.org/10.2147/OTT.S142087
Buzzoni, Roberto ; Carnaghi, Carlo ; Strosberg, Jonathan ; Fazio, Nicola ; Singh, Simron ; Herbst, Fabian ; Ridolfi, Antonia ; Pavel, Marianne E. ; Wolin, Edward M. ; Valle, Juan W. ; Oh, Do Youn ; Yao, James C. ; Pommier, Rodney. / Impact of prior therapies on everolimus activity : An exploratory analysis of RADIANT-4. In: OncoTargets and Therapy. 2017 ; Vol. 10. pp. 5013-5030.
@article{fd0af997d42049e0bb15237e97004418,
title = "Impact of prior therapies on everolimus activity: An exploratory analysis of RADIANT-4",
abstract = "Background: Recently, everolimus was shown to improve median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of lung or gastrointestinal (GI) tract compared with placebo (HR, 0.48; 95{\%} CI, 0.35–0.67; P<0.00001) in the Phase III, RADIANT-4 study. This post hoc analysis evaluates the impact of prior therapies (somatostatin analogs [SSA], chemotherapy, and radiotherapy) on everolimus activity. Trial registration: ClinicalTrials.gov identifier: NCT01524783. Patients and methods: Patients were randomized (2:1) to everolimus 10 mg/day or placebo, both with best supportive care. Subgroups of patients who received prior SSA, chemotherapy, or radiotherapy (including peptide receptor radionuclide therapy) were analyzed and reported. Results: A total of 302 patients were enrolled, of whom, 163 (54{\%}) had any prior SSA use (mostly for tumor control), 77 (25{\%}) received chemotherapy, and 63 (21{\%}) were previously exposed to radiotherapy. Patients who received everolimus had longer median PFS compared with placebo, regardless of previous SSA (with SSA: 11.1 vs 4.5 months [HR, 0.56 {95{\%} CI, 0.37–0.85}]; without SSA: 9.5 vs 3.7 months [0.57 {0.36–0.89}]), chemotherapy (with chemotherapy: 9.2 vs 2.1 months [0.35 {0.19–0.64}]; without chemotherapy: 11.2 vs 5.4 months [0.60 {0.42–0.86}]), or radiotherapy (with radiotherapy: 9.2 vs 3.0 months [0.47 {0.24–0.94}]; without radiotherapy: 11 vs 5.1 months [0.59 {0.42–0.83}]) exposure. The most frequent drug-related adverse events included stomatitis (59{\%}–65{\%}), fatigue (27{\%}–35{\%}), and diarrhea (24{\%}–34{\%}) among the subgroups. Conclusion: These results suggest that everolimus improves PFS in patients with advanced, progressive lung or GI NET, regardless of prior therapies. Safety findings were consistent with the known safety profile of everolimus in NET.",
keywords = "Chemotherapy, Neuroendocrine tumors, Progression-free survival, PRRT, Somatostatin analogs",
author = "Roberto Buzzoni and Carlo Carnaghi and Jonathan Strosberg and Nicola Fazio and Simron Singh and Fabian Herbst and Antonia Ridolfi and Pavel, {Marianne E.} and Wolin, {Edward M.} and Valle, {Juan W.} and Oh, {Do Youn} and Yao, {James C.} and Rodney Pommier",
year = "2017",
month = "10",
day = "16",
doi = "10.2147/OTT.S142087",
language = "English (US)",
volume = "10",
pages = "5013--5030",
journal = "OncoTargets and Therapy",
issn = "1178-6930",
publisher = "Dove Medical Press Ltd.",

}

TY - JOUR

T1 - Impact of prior therapies on everolimus activity

T2 - An exploratory analysis of RADIANT-4

AU - Buzzoni, Roberto

AU - Carnaghi, Carlo

AU - Strosberg, Jonathan

AU - Fazio, Nicola

AU - Singh, Simron

AU - Herbst, Fabian

AU - Ridolfi, Antonia

AU - Pavel, Marianne E.

AU - Wolin, Edward M.

AU - Valle, Juan W.

AU - Oh, Do Youn

AU - Yao, James C.

AU - Pommier, Rodney

PY - 2017/10/16

Y1 - 2017/10/16

N2 - Background: Recently, everolimus was shown to improve median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of lung or gastrointestinal (GI) tract compared with placebo (HR, 0.48; 95% CI, 0.35–0.67; P<0.00001) in the Phase III, RADIANT-4 study. This post hoc analysis evaluates the impact of prior therapies (somatostatin analogs [SSA], chemotherapy, and radiotherapy) on everolimus activity. Trial registration: ClinicalTrials.gov identifier: NCT01524783. Patients and methods: Patients were randomized (2:1) to everolimus 10 mg/day or placebo, both with best supportive care. Subgroups of patients who received prior SSA, chemotherapy, or radiotherapy (including peptide receptor radionuclide therapy) were analyzed and reported. Results: A total of 302 patients were enrolled, of whom, 163 (54%) had any prior SSA use (mostly for tumor control), 77 (25%) received chemotherapy, and 63 (21%) were previously exposed to radiotherapy. Patients who received everolimus had longer median PFS compared with placebo, regardless of previous SSA (with SSA: 11.1 vs 4.5 months [HR, 0.56 {95% CI, 0.37–0.85}]; without SSA: 9.5 vs 3.7 months [0.57 {0.36–0.89}]), chemotherapy (with chemotherapy: 9.2 vs 2.1 months [0.35 {0.19–0.64}]; without chemotherapy: 11.2 vs 5.4 months [0.60 {0.42–0.86}]), or radiotherapy (with radiotherapy: 9.2 vs 3.0 months [0.47 {0.24–0.94}]; without radiotherapy: 11 vs 5.1 months [0.59 {0.42–0.83}]) exposure. The most frequent drug-related adverse events included stomatitis (59%–65%), fatigue (27%–35%), and diarrhea (24%–34%) among the subgroups. Conclusion: These results suggest that everolimus improves PFS in patients with advanced, progressive lung or GI NET, regardless of prior therapies. Safety findings were consistent with the known safety profile of everolimus in NET.

AB - Background: Recently, everolimus was shown to improve median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of lung or gastrointestinal (GI) tract compared with placebo (HR, 0.48; 95% CI, 0.35–0.67; P<0.00001) in the Phase III, RADIANT-4 study. This post hoc analysis evaluates the impact of prior therapies (somatostatin analogs [SSA], chemotherapy, and radiotherapy) on everolimus activity. Trial registration: ClinicalTrials.gov identifier: NCT01524783. Patients and methods: Patients were randomized (2:1) to everolimus 10 mg/day or placebo, both with best supportive care. Subgroups of patients who received prior SSA, chemotherapy, or radiotherapy (including peptide receptor radionuclide therapy) were analyzed and reported. Results: A total of 302 patients were enrolled, of whom, 163 (54%) had any prior SSA use (mostly for tumor control), 77 (25%) received chemotherapy, and 63 (21%) were previously exposed to radiotherapy. Patients who received everolimus had longer median PFS compared with placebo, regardless of previous SSA (with SSA: 11.1 vs 4.5 months [HR, 0.56 {95% CI, 0.37–0.85}]; without SSA: 9.5 vs 3.7 months [0.57 {0.36–0.89}]), chemotherapy (with chemotherapy: 9.2 vs 2.1 months [0.35 {0.19–0.64}]; without chemotherapy: 11.2 vs 5.4 months [0.60 {0.42–0.86}]), or radiotherapy (with radiotherapy: 9.2 vs 3.0 months [0.47 {0.24–0.94}]; without radiotherapy: 11 vs 5.1 months [0.59 {0.42–0.83}]) exposure. The most frequent drug-related adverse events included stomatitis (59%–65%), fatigue (27%–35%), and diarrhea (24%–34%) among the subgroups. Conclusion: These results suggest that everolimus improves PFS in patients with advanced, progressive lung or GI NET, regardless of prior therapies. Safety findings were consistent with the known safety profile of everolimus in NET.

KW - Chemotherapy

KW - Neuroendocrine tumors

KW - Progression-free survival

KW - PRRT

KW - Somatostatin analogs

UR - http://www.scopus.com/inward/record.url?scp=85032284519&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032284519&partnerID=8YFLogxK

U2 - 10.2147/OTT.S142087

DO - 10.2147/OTT.S142087

M3 - Article

AN - SCOPUS:85032284519

VL - 10

SP - 5013

EP - 5030

JO - OncoTargets and Therapy

JF - OncoTargets and Therapy

SN - 1178-6930

ER -