Dieter Hörsch1, Lowell Anthony2, David J Gross3, Juan W Valle4, Staffan Welin5, Marta Benavent6, Martyn Caplin7, Marianne Pavel8, Emily Bergsland9, Kjell Öberg5, Kenneth B Kassler-Taub10, Polina Binder10, Phillip Banks10, Pablo Lapuerta10, Matthew H Kulke11. 1. Department of Gastroenterology/Endocrinology, Center for Neuroendocrine Tumors, Zentralklinik Bad Berka, Bad Berka, Germany. 2. Markey Cancer Center, University of Kentucky, Lexington, Kentucky, USA. 3. Neuroendocrine Tumor Unit, Department of Medicine, Endocrine Service, European Neuroendocrine Tumor Society Center of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 4. University of Manchester/The Christie NHS Foundation Trust, Manchester, United Kingdom. 5. Department of Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden. 6. Medical Oncology Department, Virgen del Rocío University Hospital/Instituto de Biomedicina de Sevilla, Seville, Spain. 7. Department of Gastroenterology & Hepatobiliary Medicine, Royal Free Hospital, Pond Street Centre for Gastroenterology, London, United Kingdom. 8. Department of Gastroenterology and Hepatology, Charité-Universitätsmedizin, Berlin, Germany. 9. Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California, USA. 10. Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA. 11. Section of Hematology/Oncology, Boston University and Boston Medical Center, Boston, Massachusetts, USA.
Abstract
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).
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).
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