Weight Maintenance up to 48 Weeks in Patients With Carcinoid Syndrome Treated With Telotristat Ethyl: Pooled Data From the Open-Label Extensions of the Phase III Clinical Trials TELESTAR and TELECAST

Rajaventhan Srirajaskanthan,Marianne Pavel,Matthew Kulke,Dominique Clement,Aude Houchard,Lucie Keeber,Martin O Weickert

doi:10.1016/j.clinthera.2021.08.014

Abstract

Reported incidences of neuroendocrine tumors (NETs) appear to be increasing, possibly due to greater disease awareness and increased accuracy of diagnosis. Approximately 20% of patients with NETs develop carcinoid syndrome (CS), which arises from elevated secretion of bioactive compounds, including serotonin, from NETs. This leads to symptoms including diarrhea and flushing, which result in weight loss and are associated with considerable negative impact on patients’ quality of life. We previously reported significant weight gain and improved nutritional status in patients with NETs who were treated with telotristat ethyl (TE) for 12 weeks. In this follow-up analysis, using pooled data from the 36-week open-label extensions of the TELESTAR (NCT01677910) and TELECAST (NCT02063659) phase III trials, we demonstrate that improvements in weight and nutritional parameters were sustained or further improved in patients with CS through to week 48 of treatment with TE. At week 48/end of study, 68.7% of all patients maintained a stable weight or had weight gain and the mean changes from baseline in cholesterol and albumin levels in patients treated with TE were +0.41 mmol/L and -0.34 g/L, respectively. These results indicate that TE, alongside routine clinical practice, may provide long-term benefits in nutritional intake and weight evolution in patients with CS.

Highlights

This communication provides an assessment of longterm weight changes and nutritional parameters in patients with carcinoid syndrome (CS) treated with telotristat ethyl (TE).Neuroendocrine tumors (NETs) are rare, reported incidences appear to be increasing, partly due to greater disease awareness and increased accuracy of diagnosis.[1,2] Functioning NETs are clinically symptomatic and typically characterized by the hormones they secrete;[2] patients often present with symptoms including diarrhea and flushing.[3]
We previously reported significant weight gain and improved nutritional parameters in patients treated with TE in the 12-week double-blind period of the TELESTAR trial.[16]
211 patients were enrolled across TELESTAR (N = 135) and TELECAST (N = 76) and randomized to TE 250 mg (n = 70), TE 500 mg (n = 70), or placebo (n = 71)

Summary

Introduction

This communication provides an assessment of longterm weight changes and nutritional parameters in patients with carcinoid syndrome (CS) treated with telotristat ethyl (TE).Neuroendocrine tumors (NETs) are rare, reported incidences appear to be increasing, partly due to greater disease awareness and increased accuracy of diagnosis.[1,2] Functioning NETs are clinically symptomatic and typically characterized by the hormones they secrete;[2] patients often present with symptoms including diarrhea and flushing.[3]. Clinical Therapeutics advanced stages, with symptoms such as weight loss, bleeding, or abdominal pain, resulting from increased tumor mass and metastases.[4,5]. 20% of patients with NETs develop CS.[6] CS arises from elevated secretion of bioactive compounds, including serotonin, from NETs, leading to symptoms including diarrhea and flushing episodes, abdominal pain, or bronchoconstriction.[7] These symptoms are all associated with considerable negative impact on patients’ quality of life.[2,8] In particular, diarrhea and flushing, resulting in weight loss, have been identified as the largest contributors to impaired quality of life in these patients.[9,10]

Methods

Results

Conclusion