Telotristat ethyl in carcinoid syndrome: Safety and efficacy in the TELECAST phase 3 trial

Marianne Pavel, David J. Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R.P. Warner, Matthew H. Kulke, Lowell B. Anthony, Pamela L. Kunz, Dieter Hörsch, Martin O. Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio Garcia-Carbonero

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing >4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs (or >1 symptom or >4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. Through week 12, TEAEs were generally mild to moderate in severity; 5 (placebo), 1 (telotristat ethyl 250 mg) and 3 (telotristat ethyl 500 mg) patients experienced serious events, and the rate of TEAEs in the OLE was comparable. At week 12, significant reductions in u5-HIAA from baseline were observed, with Hodges-Lehmann estimators of median treatment differences from placebo of -54.0% (95% confidence limits, -85.0%, -25.1%, P < 0.001) and -89.7% (95% confidence limits, -113.1%, -63.9%, P < 0.001) for telotristat ethyl 250 mg and 500 mg. These results support the safety and efficacy of telotristat ethyl when added to SSAs in patients with CS diarrhea (ClinicalTrials.gov identifier: NCT02063659).

Original languageEnglish
Pages (from-to)309-322
Number of pages14
JournalEndocrine-Related Cancer
Volume25
Issue number3
DOIs
StatePublished - Mar 2018

Bibliographical note

Funding Information:
M P reports personal fees from Lexicon Pharmaceuticals, Inc., Ipsen Pharmaceuticals, Inc., and Novartis Pharmaceuticals, Inc., outside the submitted work. P P reports payments to Newcastle upon Tyne Hospitals NHS Foundation Trust from Lexicon Pharmaceuticals, Inc., to cover research costs for recruiting and conducting the study. R S reports grants from Ipsen Pharmaceuticals, Inc., and Novartis Pharmaceuticals, Inc., outside of the submitted work. R R P W reports clinical trial support from Lexicon Pharmaceuticals, Inc., during the study. P L K reports grants and personal fees from Lexicon Pharmaceuticals, Inc., during the study, along with grants from Advanced Accelerator Applications, Dicerna, Esanex, Genentech, Merck, Oxigene, and Incyte and grants and personal fees from Ipsen Pharmaceuticals, Inc, and Novartis Pharmaceuticals, Inc., outside of the submitted work. D H reports personal fees from Lexicon Pharmaceuticals, Inc., and personal fees and grants from Ipsen Pharmaceuticals, Inc., during the course of the study, along with personal fees from Lexicon

Funding Information:
Pharmaceuticals, Inc., grants and personal fees from Ipsen Pharmaceuticals, Inc., Novartis Pharmaceuticals, Inc. and Pfizer Pharmaceuticals, Inc., outside of the submitted work. MOW reports personal fees from Ipsen Pharmaceuticals, Inc., and Novartis Pharmaceuticals, Inc., and grants from Pfizer outside the submitted work. P L, W J, K K-T, S W and R F are employees of Lexicon Pharmaceuticals, Inc., which may include compensation that includes stock in Lexicon Pharmaceuticals, Inc. D J G, M B, L B A and R G-C have nothing to disclose.

Funding Information:
This work was supported by Lexicon Pharmaceuticals, Inc., The Woodlands, TX, USA. Employees of the company were involved in the study design; the collection, analysis and interpretation of data; the writing and review of the manuscript; and the decision to submit for publication.

Publisher Copyright:
© 2018 The authors.

Keywords

  • 5-HIAA
  • Carcinoid syndrome
  • Metastatic neuroendocrine tumor
  • Serotonin
  • Somatostatin analog

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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