BIOCHEMICAL RESPONSES IN SYMPTOMATIC AND ASYMPTOMATIC PATIENTS WITH NEUROENDOCRINE TUMORS: POOLED ANALYSIS OF 2 PHASE 3 TRIALS

Mirakhur B, Pavel ME, Pommier RF, Fisher GA, Phan AT, Massien C, Liyanage N, Lowenthal SP, Vinik A (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Endocrine Practice American Association of Clinical Endocrinology

Book Volume: 24

Pages Range: 948-962

Journal Issue: 11

DOI: 10.4158/EP-2018-0296

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. ABBREVIATIONS: 5-HIAA = 5-hydroxyindoleacetic acid; CgA = chromogranin A; CI = confidence interval; CLARINET = Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors; CS = carcinoid syndrome; ELECT = Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment; HR = hazard ratio; ITT = intention-to-treat; NET = neuroendocrine tumor; PanNET = pancreatic NET; PFS = progression-free survival; PPI = proton pump inhibitor; SSA = somatostatin analogue; ULN = upper limit of normal.

Authors with CRIS profile

Marianne Ellen Pavel Professur für Endokrinologie

Involved external institutions

Ipsen Pharma FR France (FR) Stanford University US United States (USA) (US) Ipsen Biopharmaceuticals, Inc. US United States (USA) (US) Morehouse School of Medicine US United States (USA) (US) Eastern Virginia Medical School US United States (USA) (US) Oregon Health and Science University (OSHU) US United States (USA) (US)

How to cite

APA:

Mirakhur, B., Pavel, M.E., Pommier, R.F., Fisher, G.A., Phan, A.T., Massien, C.,... Vinik, A. (2018). BIOCHEMICAL RESPONSES IN SYMPTOMATIC AND ASYMPTOMATIC PATIENTS WITH NEUROENDOCRINE TUMORS: POOLED ANALYSIS OF 2 PHASE 3 TRIALS. Endocrine Practice, 24(11), 948-962. https://dx.doi.org/10.4158/EP-2018-0296

MLA:

Mirakhur, Beloo, et al. "BIOCHEMICAL RESPONSES IN SYMPTOMATIC AND ASYMPTOMATIC PATIENTS WITH NEUROENDOCRINE TUMORS: POOLED ANALYSIS OF 2 PHASE 3 TRIALS." Endocrine Practice 24.11 (2018): 948-962.

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