PMID- 33940581 OWN - NLM STAT- MEDLINE DCOM- 20220407 LR - 20220408 IS - 1423-0194 (Electronic) IS - 0028-3835 (Print) IS - 0028-3835 (Linking) VI - 112 IP - 3 DP - 2022 TI - Long-Term Treatment with Telotristat Ethyl in Patients with Carcinoid Syndrome Symptoms: Results from the TELEPATH Study. PG - 298-310 LID - 10.1159/000516958 [doi] AB - INTRODUCTION: Telotristat ethyl is indicated for use in combination with somatostatin analogs (SSAs) to treat carcinoid syndrome (CS) diarrhea uncontrolled by SSAs alone in adults, but long-term safety and efficacy data beyond 48 weeks are needed. OBJECTIVES: The aims of the study were to evaluate the long-term safety and tolerability of telotristat ethyl and its effect on quality of life (QOL) in patients with CS. METHODS: In this phase 3, nonrandomized, multicenter, open-label, long-term extension study (TELEPATH), patients who participated in phase 2 or 3 trials of telotristat ethyl continued treatment at their present dose level (250 or 500 mg thrice daily) for 84 weeks. Safety and tolerability, the primary endpoint, were assessed by monitoring adverse events (AEs), serious AEs, AEs of special interest (AESIs; including liver-related AEs, depression, and gastrointestinal AEs), and deaths. The secondary objective was to evaluate changes in patients' QOL using validated cancer questionnaires and a subjective global assessment of CS symptoms. RESULTS: In 124 patients exposed to telotristat ethyl for a mean of 102.6 +/- 53.2 weeks, the type and frequency of AEs were consistent with those reported in previous trials. The occurrence of AESIs was not related to dosage or duration of therapy. Most AEs were mild to moderate in severity, and no deaths were related to telotristat ethyl. QOL scores remained stable, and the majority of patients reported adequate symptom relief throughout the study. CONCLUSIONS: Safety results of TELEPATH support the long-term use of telotristat ethyl in patients with CS diarrhea. Telotristat ethyl was well-tolerated and associated with sustained improvement in QOL scores (NCT02026063). CI - (c) 2021 The Author(s) Published by S. Karger AG, Basel. FAU - Horsch, Dieter AU - Horsch D AD - Department of Gastroenterology/Endocrinology, Center for Neuroendocrine Tumors, Zentralklinik Bad Berka, Bad Berka, Germany. FAU - Anthony, Lowell AU - Anthony L AD - Markey Cancer Center, University of Kentucky, Lexington, Kentucky, USA. FAU - Gross, David J AU - Gross DJ AD - Neuroendocrine Tumor Unit, Department of Medicine, Endocrine Service, European Neuroendocrine Tumor Society Center of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. FAU - Valle, Juan W AU - Valle JW AD - University of Manchester/The Christie NHS Foundation Trust, Manchester, United Kingdom. FAU - Welin, Staffan AU - Welin S AD - Department of Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden. FAU - Benavent, Marta AU - Benavent M AD - Medical Oncology Department, Virgen del Rocio University Hospital/Instituto de Biomedicina de Sevilla, Seville, Spain. FAU - Caplin, Martyn AU - Caplin M AD - Department of Gastroenterology & Hepatobiliary Medicine, Royal Free Hospital, Pond Street Centre for Gastroenterology, London, United Kingdom. FAU - Pavel, Marianne AU - Pavel M AD - Department of Gastroenterology and Hepatology, Charite-Universitatsmedizin, Berlin, Germany. FAU - Bergsland, Emily AU - Bergsland E AD - Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California, USA. FAU - Oberg, Kjell AU - Oberg K AD - Department of Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden. FAU - Kassler-Taub, Kenneth B AU - Kassler-Taub KB AD - Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA. FAU - Binder, Polina AU - Binder P AD - Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA. FAU - Banks, Phillip AU - Banks P AD - Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA. FAU - Lapuerta, Pablo AU - Lapuerta P AD - Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA. FAU - Kulke, Matthew H AU - Kulke MH AD - Section of Hematology/Oncology, Boston University and Boston Medical Center, Boston, Massachusetts, USA. LA - eng SI - ClinicalTrials.gov/NCT02026063 PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20210503 PL - Switzerland TA - Neuroendocrinology JT - Neuroendocrinology JID - 0035665 RN - 0 (Pyrimidines) RN - 47E5O17Y3R (Phenylalanine) RN - 8G388563M7 (telotristat ethyl) SB - IM MH - Adult MH - Humans MH - *Malignant Carcinoid Syndrome/drug therapy MH - Phenylalanine/adverse effects/analogs & derivatives MH - Pyrimidines MH - *Quality of Life MH - Treatment Outcome PMC - PMC8985007 OTO - NOTNLM OT - Carcinoid syndrome OT - Diarrhea OT - Quality of life OT - Safety and tolerability OT - Telotristat ethyl COIS- Dieter Horsch has received personal fees and grants from Lexicon Pharmaceuticals, Inc.; Ipsen Pharmaceuticals, Inc.; Novartis Pharmaceuticals, Inc.; and Pfizer Pharmaceuticals, Inc., and advisory board honoraria from Advanz Pharma USA. Lowell Anthony has received honoraria for advisory boards from Lexicon, AbbVie, Curium, and Sun Pharma, and his institution has received grants from Lexicon and Entrinsic Health Solutions. David J. Gross has no financial interests to declare. Juan W. Valle has received personal fees from Agios, AstraZeneca, Debiopharm, Delcath Systems, Genoscience Pharma, Imaging Equipment Limited, Incyte, Ipsen, Keocyt, Merck, Mundipharma EDO, Novartis, PCI Biotech, Pieris Pharmaceuticals, QED, and Wren Laboratories, as well as grants, personal fees, and nonfinancial support from NuCana; personal fees and nonfinancial support from Pfizer; and grants and personal fees from Servier, all outside the submitted work. Staffan Welin has no financial interests to declare. Marta Benavent has received honoraria for advisory boards, meetings, and/or lectures from Novartis, Ipsen, Roche, and Pfizer. Martyn Caplin has received advisory board and speaker honoraria from AAA, Ipsen, Lexicon, Novartis, and Pfizer. Marianne Pavel has received honoraria for consultancy and presentations from Lexicon, Novartis, Ipsen, AAA, Boehringer Ingelheim, Pfizer, Keocyt, Riemser, and Prime Oncology and grants for research from Ipsen and Novartis. Emily Bergsland receives royalties from UpToDate. Kjell Oberg has no financial interests to disclose. Kenneth B. Kassler-Taub and Phillip Banks are employed by Lexicon Pharmaceuticals and hold stock in the company. Polina Binder and Pablo Lapuerta were employed by Lexicon Pharmaceuticals and held stock in the company at the time the research was conducted and the manuscript was written. Matthew H. Kulke has no financial interests to disclose. EDAT- 2021/05/04 06:00 MHDA- 2022/04/08 06:00 PMCR- 2021/05/03 CRDT- 2021/05/03 20:30 PHST- 2020/10/07 00:00 [received] PHST- 2021/04/27 00:00 [accepted] PHST- 2021/05/04 06:00 [pubmed] PHST- 2022/04/08 06:00 [medline] PHST- 2021/05/03 20:30 [entrez] PHST- 2021/05/03 00:00 [pmc-release] AID - 000516958 [pii] AID - nen-0112-0298 [pii] AID - 10.1159/000516958 [doi] PST - ppublish SO - Neuroendocrinology. 2022;112(3):298-310. doi: 10.1159/000516958. Epub 2021 May 3.