ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 52 P14 | DOI: 10.1530/endoabs.52.P14

Efficacy and safety of telotristat ethyl in patients with carcinoid syndrome inadequately controlled by somatostatin analogs: Analysis of the completed TELESTAR extension period

D Horsch1, MH Kulke2, M Caplin3, L Anthony4, E Bergsland5, K Oberg6, R Warner7, P Kunz8, E Grande Pulido9, J Valle10, J Dillon11, P Lapuerta12, P Banks12, S Jackson12 & M Pavel13

1Department of Internal Medicine, Zentralklinik Bad Berka, Bad Berka, Germany; 2Division of Medical Oncology/Solid Tumor Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; 3Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK; 4Division of Medical Oncology, University of Kentucky, Lexington, Kentucky, USA; 5Hereditary GI Cancer Prevention Program, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA; 6Department of Endocrine Oncology, Uppsala University, Uppsala, Sweden; 7Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; 8Division of Oncology, Stanford University Medical Center, Stanford, California, USA; 9Department of Medical Oncology, Hospital Ramon y Cajal, Madrid, Spain; 10Department of Medical Oncology, The University of Manchester/The Christie, Manchester, UK; 11Department of Internal Medicine, Endocrinology and Metabolism, University of Iowa, Iowa City, Iowa, USA; 12Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA; 13Department of Gastroenterology and Hepatology, Endocrinology & Metabolic Diseases, Charite-Universitatsmedizin, Berlin, Germany.

Background: The phase III, placebo-controlled, randomized TELESTAR study evaluated efficacy and safety of telotristat ethyl (TE) in patients (pts) with diarrhoea (≥4 bowel movements (BMs)/day) due to carcinoid syndrome (CS) inadequately controlled by somatostatin analogs (SSAs). TE, a tryptophan hydroxylase inhibitor, decreases peripheral serotonin levels. As add-on treatment to SSAs, TE 250 mg 3x/day (tid) and TE 500 mg tid significantly reduced BM frequency (P<0.001) compared with placebo over the 12-week Double-blind Treatment (DBT) period. After Week 12, pts crossed over to a 36 week Open-label Extension (OLE) period with TE 500 mg tid; data from the full 48 weeks are presented.

Methods: Changes from baseline in BM frequency (monitored weekly), urinary 5-hydroxyindoleacetic acid (u5-HIAA; Weeks 18, 24, and 48), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTCQLQC30) score (Weeks 24 and 48), and safety during the OLE period were evaluated.

Results: Of the 135 pts randomly assigned, 118 completed the DBT period; 115 pts subsequently entered (and 79 completed) the OLE period. Of the 36 pts who discontinued the OLE period, the most frequent reasons were adverse event (AE; 15 pts) and withdrawal of consent (9 pts). Treatment-emergent AEs led 18 pts to discontinue TE; gastrointestinal disorder was the most commonly reported reason (6 pts). Reductions from baseline in BM frequency (~2 BMs/day) and u5-HIAA levels (range −20.0 mg to −49.5 mg/24 hours) during the OLE were consistent with results of the DBT period and persisted through Week 48. Improvement in EORTCQLQ-C30 diarrhea subscale scores relative to baseline (range −18.8 to −30.6 points) was notable and persisted through Week 48. Crossover into the OLE period was well tolerated. Treatment-emergent AEs were mainly mild to moderate and occurred at a similar rate as in the DBT period.

Conclusions: Patients benefitted from TE throughout the OLE period. TE was well tolerated over 48 weeks and its efficacy was consistent with previously reported data.