Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome

M. O. Weickert; Gregory Kaltsas; Dieter Hörsch; Pablo Lapuerta; Marianne Pavel; Juan Valle; Martyn E Caplin; Emily Bergsland; Pamela L. Kunz; Lowell B. Anthony; Enrique Grande; Kjell Öberg; Staffan Welin; Catherine Lombard-Bohas; J. K. Ramage; Ashwin Kittur; Qi Yang; Matthew H Kulke

doi:10.1016/j.clinthera.2018.04.006

Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome

M. O. Weickert, Gregory Kaltsas, Dieter Hörsch, Pablo Lapuerta, Marianne Pavel, Juan Valle, Martyn E Caplin, Emily Bergsland, Pamela L. Kunz, Lowell B. Anthony, Enrique Grande, Kjell Öberg, Staffan Welin, Catherine Lombard-Bohas, J. K. Ramage, Ashwin Kittur, Qi Yang, Matthew H Kulke

Division of Cancer Sciences (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

Purpose

In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m2) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.

Methods

Assessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan.

Findings

In 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss ≥3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.

Implications

Up to 32.5% of patients treated with telotristat ethyl experienced significant, dose-dependent weight gain, associated with reduced diarrhea severity and improved biochemical and metabolic parameters. Improved nutritional status could be an additional aspect of telotristat ethyl efficacy among patients with functioning metastatic neuroendocrine tumors.

Original language	English
Journal	Clinical Therapeutics
Early online date	1 May 2018
DOIs	https://doi.org/10.1016/j.clinthera.2018.04.006
Publication status	Published - 2018

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.clinthera.2018.04.006Licence: CC BY-NC-ND

Cite this

Weickert, M. O., Kaltsas, G., Hörsch, D., Lapuerta, P., Pavel, M., Valle, J., Caplin, M. E., Bergsland, E., Kunz, P. L., Anthony, L. B., Grande, E., Öberg, K., Welin, S., Lombard-Bohas, C., Ramage, J. K., Kittur, A., Yang, Q., & Kulke, M. H. (2018). Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome. Clinical Therapeutics. https://doi.org/10.1016/j.clinthera.2018.04.006

@article{8f725fdfee064656be6a7f7a14225590,

title = "Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome",

abstract = "PurposeIn the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m2) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.MethodsAssessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan.FindingsIn 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss ≥3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.ImplicationsUp to 32.5% of patients treated with telotristat ethyl experienced significant, dose-dependent weight gain, associated with reduced diarrhea severity and improved biochemical and metabolic parameters. Improved nutritional status could be an additional aspect of telotristat ethyl efficacy among patients with functioning metastatic neuroendocrine tumors.",

author = "Weickert, {M. O.} and Gregory Kaltsas and Dieter H{\"o}rsch and Pablo Lapuerta and Marianne Pavel and Juan Valle and Caplin, {Martyn E} and Emily Bergsland and Kunz, {Pamela L.} and Anthony, {Lowell B.} and Enrique Grande and Kjell {\"O}berg and Staffan Welin and Catherine Lombard-Bohas and Ramage, {J. K.} and Ashwin Kittur and Qi Yang and Kulke, {Matthew H}",

year = "2018",

doi = "10.1016/j.clinthera.2018.04.006",

language = "English",

journal = "Clinical Therapeutics",

issn = "0149-2918",

publisher = "Elsevier BV",

}

Weickert, MO, Kaltsas, G, Hörsch, D, Lapuerta, P, Pavel, M, Valle, J, Caplin, ME, Bergsland, E, Kunz, PL, Anthony, LB, Grande, E, Öberg, K, Welin, S, Lombard-Bohas, C, Ramage, JK, Kittur, A, Yang, Q & Kulke, MH 2018, 'Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome', Clinical Therapeutics. https://doi.org/10.1016/j.clinthera.2018.04.006

TY - JOUR

T1 - Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome

AU - Weickert, M. O.

AU - Kaltsas, Gregory

AU - Hörsch, Dieter

AU - Lapuerta, Pablo

AU - Pavel, Marianne

AU - Valle, Juan

AU - Caplin, Martyn E

AU - Bergsland, Emily

AU - Kunz, Pamela L.

AU - Anthony, Lowell B.

AU - Grande, Enrique

AU - Öberg, Kjell

AU - Welin, Staffan

AU - Lombard-Bohas, Catherine

AU - Ramage, J. K.

AU - Kittur, Ashwin

AU - Yang, Qi

AU - Kulke, Matthew H

PY - 2018

Y1 - 2018

N2 - PurposeIn the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m2) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.MethodsAssessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan.FindingsIn 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss ≥3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.ImplicationsUp to 32.5% of patients treated with telotristat ethyl experienced significant, dose-dependent weight gain, associated with reduced diarrhea severity and improved biochemical and metabolic parameters. Improved nutritional status could be an additional aspect of telotristat ethyl efficacy among patients with functioning metastatic neuroendocrine tumors.

AB - PurposeIn the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m2) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.MethodsAssessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan.FindingsIn 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss ≥3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.ImplicationsUp to 32.5% of patients treated with telotristat ethyl experienced significant, dose-dependent weight gain, associated with reduced diarrhea severity and improved biochemical and metabolic parameters. Improved nutritional status could be an additional aspect of telotristat ethyl efficacy among patients with functioning metastatic neuroendocrine tumors.

U2 - 10.1016/j.clinthera.2018.04.006

DO - 10.1016/j.clinthera.2018.04.006

M3 - Article

SN - 0149-2918

JO - Clinical Therapeutics

JF - Clinical Therapeutics

ER -

Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome

Abstract

Research Beacons, Institutes and Platforms

UN SDGs

Access to Document

Fingerprint

Cite this