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

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    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

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    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

    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{507bfe0054b94bfab881124738360c01,
    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",
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    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

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