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

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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

    Keywords

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

    ASJC Scopus subject areas

    • Oncology
    • Pharmacology (medical)

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  • Cite this

    Buzzoni, R., Carnaghi, C., Strosberg, J., Fazio, N., Singh, S., Herbst, F., Ridolfi, A., Pavel, M. E., Wolin, E. M., Valle, J. W., Oh, D. Y., Yao, J. C., & 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