Changes in Carcinoid Syndrome Symptoms Among Patients Receiving Telotristat Ethyl in US Clinical Practice: Findings from the TELEPRO-II Real-World Study

Abstract

Background

Inadequately controlled symptoms incur a substantial burden on patients with neuroendocrine tumors and carcinoid syndrome (CS). The effectiveness of telotristat ethyl (TE) with a somatostatin analog for uncontrolled CS diarrhea has been demonstrated in clinical trials and observational studies. TELEPRO-II was a prospective observational study evaluating TE’s effectiveness in clinical practice over the first 3 months of treatment.

Methods

Patients initiating TE in 2018 participated in an optional nurse support program reporting CS symptoms during interviews at baseline and 1, 2, and 3 months after TE initiation. Eligible patients received TE for ≥3 months and reported symptom burden at baseline and ≥1 follow-up visit within the first 3 months. Daily bowel movement (BM) frequency and flushing episodes were reported as events/episodes per day. Stool consistency, nausea severity, urgency severity, and abdominal pain were reported on a severity scale (1–10). Symptom changes were evaluated using paired-sample t-tests and Wilcoxon signed-rank tests. Analysis of symptoms based on achievement of <30% or ≥30% reduction in daily BM frequency was conducted using a cumulative distribution function.

Results

A total of 684/1603 (43%) patients were eligible for analysis. At baseline, patients reported a mean of 6.3 BM/day, nausea severity of 8.4/10 and stool urgency of 8.2/10. Significant improvements in all CS symptoms were observed after 3 months of TE. Mean daily BMs were reduced 64% after 3 months of TE (mean reduction [SD], –3.99 [3.8]; P<0.0001). Most patients (74%, n=503) reported ≥30% reduction in daily BM frequency; these patients also reported improvements in other symptoms (76–87%). Patients with <30% reduction in daily BMs also reported improvements in nausea severity (62%, n=24), daily flushing episodes (66%, n=98), abdominal pain (50%, n=60), urgency severity (38%, n=64), and stool consistency (24%, n=44).

Conclusion

Patients treated with TE in a real-world setting experienced significant, clinically meaningful improvements in CS symptoms.

Keywords:

• carcinoid syndrome
• carcinoid syndrome diarrhea
• neuroendocrine tumor
• telotristat ethyl
• somatostatin analog

Acknowledgments

This work was supported by TerSera Therapeutics. The authors wish to thank Neha Kapur and Salma Sayeed for their review of the manuscript. Medical writing support was provided by Jeff Frimpter, MPH, funded by TerSera Therapeutics.

Authors’ Responsibility

The authors confirm they have not previously published or submitted this manuscript elsewhere; they took a significant part in the work and approved the final version of the manuscripts; they have complied with ethical standards; they agree AME Publishing Company to get a license to publish the accepted article when the manuscript is accepted; and they have obtained all necessary permissions to publish any figures or tables in the manuscript, and assure that the authors will pay for any necessary charges.

Ethical Statement

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki in a de-identified dataset with no patient identifiers, and determined to be exempt from Institutional Review Board oversight (Advarra^®, Columbia, MD).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

MHK and HFK received research support from Lexicon Pharmaceuticals, Inc. and TerSera Therapeutics. KM was employed by DataWave Solutions which received research funding from Lexicon Pharmaceuticals, Inc. and TerSera Therapeutics. VNJ was employed by Lexicon Pharmaceuticals, Inc. and TerSera Therapeutics. The authors report no other conflicts of interest in this work.