Long-Term Treatment with Telotristat Ethyl in Patients with Carcinoid Syndrome Symptoms: Results from the TELEPATH Study

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).

Keywords: Carcinoid syndrome; Diarrhea; Quality of life; Safety and tolerability; Telotristat ethyl.

Conflict of interest statement

Dieter Hörsch 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 Öberg 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.

© 2021 The Author(s) Published by S. Karger AG, Basel.

Figures

Fig. 1

Patient disposition. Patients entered the open-label extension on the same dose level of telotristat ethyl that they received during the parent trial. AE, adverse event; TID, 3 times daily.

Fig. 2

LS mean change from baseline in global health status and QOL assessments of CS symptoms by study visit in the per-protocol population. a Global health status/QOL subscale of the EORTC QLQ C30. b GI symptoms subscale of the GI.NET21. Error bars represent 95% CIs. EORTC, European Organisation for Research and Treatment of Cancer; GI.NET21, Gastrointestinal Symptoms of Carcinoid Neuroendocrine Tumors; LS, least square; QOL, quality of life; GI, gastrointestinal; CI, confidence interval; CS, carcinoid syndrome.

Fig. 3

Percentage of patients receiving telotristat ethyl who reported adequate relief of GI CS symptoms over the study period. GI, gastrointestinal; CS, carcinoid syndrome.