Biochemical responses in symptomatic and asymptomatic patients with neuroendocrine tumors

Pooled analysis of two phase 3 trials

Beloo Mirakhur, Marianne E. Pavel, Rodney Pommier, George A. Fisher, Alexandria T. Phan, Christine Massien, Nilani Liyanage, Susan Pitman Lowenthal, Aaron I. Vinik

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    Objective: Neuroendocrine tumors (NETs) are associated with elevated 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA) levels. This study aimed to analyze relationships between urinary 5-HIAA and plasma CgA levels and clinical outcomes. Methods: Centrally assessed biomarker levels and correlations with progression-free survival (PFS) and carcinoid syndrome (CS) symptom control were evaluated in a pooled analysis of CLARINET (96-week randomized, double-blind, placebo-controlled) and ELECT (16-week randomized, double-blind, placebo-controlled, 32-week initial open label and ≥2 year long-term extension open label) studies of adults with NETs, with (ELECT) or without (CLARINET) CS at 97 institutions. Patients were treated with subcutaneous lanreotide depot 120 mg monthly. Results: Of 319 pooled patients, 86% and 95% had baseline 5-HIAA and CgA data, respectively, with 47% and 74% having levels greater than the upper limit of normal (ULN). PFS was longer among patients who experienced a decrease in biomarker levels at week 12, with statistical significance reached in the CgA cohort (not reached vs. 14.4 months; P<.0001). A large proportion (87%) of patients without symptoms of CS in the CLARINET study had detectable levels of 5-HIAA (48% >ULN). In ELECT, patients with CS who received lanreotide and experienced a biochemical response (≥50% decrease from baseline) achieved greater symptom control. Conclusion: This pooled analysis of two randomized, placebo-controlled trials demonstrated that 5-HIAA and CgA are secreted as biochemical biomarkers in many patients with NETs, regardless of clinical syndromes. Significant biochemical response was associated with improved clinical outcomes, as measured by improved PFS or improved CS symptom control.

    Original languageEnglish (US)
    Pages (from-to)948-962
    Number of pages15
    JournalEndocrine Practice
    Volume24
    Issue number11
    DOIs
    StatePublished - Nov 1 2018

    Fingerprint

    Chromogranin A
    Neuroendocrine Tumors
    Hydroxyindoleacetic Acid
    Carcinoid Tumor
    Disease-Free Survival
    Biomarkers
    Placebos
    Randomized Controlled Trials

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology

    Cite this

    Biochemical responses in symptomatic and asymptomatic patients with neuroendocrine tumors : Pooled analysis of two phase 3 trials. / Mirakhur, Beloo; Pavel, Marianne E.; Pommier, Rodney; Fisher, George A.; Phan, Alexandria T.; Massien, Christine; Liyanage, Nilani; Lowenthal, Susan Pitman; Vinik, Aaron I.

    In: Endocrine Practice, Vol. 24, No. 11, 01.11.2018, p. 948-962.

    Research output: Contribution to journalArticle

    Mirakhur, B, Pavel, ME, Pommier, R, Fisher, GA, Phan, AT, Massien, C, Liyanage, N, Lowenthal, SP & Vinik, AI 2018, 'Biochemical responses in symptomatic and asymptomatic patients with neuroendocrine tumors: Pooled analysis of two phase 3 trials', Endocrine Practice, vol. 24, no. 11, pp. 948-962. https://doi.org/10.4158/EP-2018-0296
    Mirakhur, Beloo ; Pavel, Marianne E. ; Pommier, Rodney ; Fisher, George A. ; Phan, Alexandria T. ; Massien, Christine ; Liyanage, Nilani ; Lowenthal, Susan Pitman ; Vinik, Aaron I. / Biochemical responses in symptomatic and asymptomatic patients with neuroendocrine tumors : Pooled analysis of two phase 3 trials. In: Endocrine Practice. 2018 ; Vol. 24, No. 11. pp. 948-962.
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    abstract = "Objective: Neuroendocrine tumors (NETs) are associated with elevated 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA) levels. This study aimed to analyze relationships between urinary 5-HIAA and plasma CgA levels and clinical outcomes. Methods: Centrally assessed biomarker levels and correlations with progression-free survival (PFS) and carcinoid syndrome (CS) symptom control were evaluated in a pooled analysis of CLARINET (96-week randomized, double-blind, placebo-controlled) and ELECT (16-week randomized, double-blind, placebo-controlled, 32-week initial open label and ≥2 year long-term extension open label) studies of adults with NETs, with (ELECT) or without (CLARINET) CS at 97 institutions. Patients were treated with subcutaneous lanreotide depot 120 mg monthly. Results: Of 319 pooled patients, 86{\%} and 95{\%} had baseline 5-HIAA and CgA data, respectively, with 47{\%} and 74{\%} having levels greater than the upper limit of normal (ULN). PFS was longer among patients who experienced a decrease in biomarker levels at week 12, with statistical significance reached in the CgA cohort (not reached vs. 14.4 months; P<.0001). A large proportion (87{\%}) of patients without symptoms of CS in the CLARINET study had detectable levels of 5-HIAA (48{\%} >ULN). In ELECT, patients with CS who received lanreotide and experienced a biochemical response (≥50{\%} decrease from baseline) achieved greater symptom control. Conclusion: This pooled analysis of two randomized, placebo-controlled trials demonstrated that 5-HIAA and CgA are secreted as biochemical biomarkers in many patients with NETs, regardless of clinical syndromes. Significant biochemical response was associated with improved clinical outcomes, as measured by improved PFS or improved CS symptom control.",
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    T2 - Pooled analysis of two phase 3 trials

    AU - Mirakhur, Beloo

    AU - Pavel, Marianne E.

    AU - Pommier, Rodney

    AU - Fisher, George A.

    AU - Phan, Alexandria T.

    AU - Massien, Christine

    AU - Liyanage, Nilani

    AU - Lowenthal, Susan Pitman

    AU - Vinik, Aaron I.

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