Telotristat ethyl: a new option for the management of carcinoid syndrome

ABSTRACT

Introduction: Many patients with neuroendocrine tumour-related carcinoid syndrome treated with somatostatin analogues (SSA) won’t achieve adequate symptom relief with the SSA alone; new treatment options are required. Telotristat ethyl is a tryptophan hydroxylase inhibitor, developed for the treatment of carcinoid syndrome.

Areas covered: This review summarises the evidence supporting the role of telotristat ethyl in the management of carcinoid syndrome. Rationale, pharmacodynamics, pharmacokinetics, metabolism, clinical experience, efficacy and toxicity profiles are covered.

Expert opinion: The efficacy of telotristat ethyl in producing a statistically-significant and clinically-meaningful reduction in daily bowel movements has been confirmed in phase III clinical trials. Two pivotal trials, TELESTAR and TELECAST, explored the role of telotristat ethyl in the management of patients with carcinoid syndrome refractory to SSAs focusing on patients with ≥4 and <4 daily bowel movements, respectively. In addition, benefit was confirmed in patient-reported outcomes. Based on activity and safe toxicity profile, telotristat ethyl is pending regulatory agencies evaluation and is likely to add to the armamentarium used to treat carcinoid syndrome. Long-term safety and efficacy data will be available from the ongoing TELEPATH study. The impact on carcinoid heart disease, mesenteric fibrosis and other long-term complications of carcinoid syndrome as well as its role earlier in patients’ pathways remain investigational.

KEYWORDS:

• Bowel movement
• carcinoid syndrome
• diarrhoea
• flushing
• LX1606
• neuroendocrine tumours
• serotonin synthesis inhibitor
• telotristat ethyl
• tryptophan hydroxylase 1 (Tph1)

Declaration of interest

JW Valle has received Honoraria and a Travel Grant from Ipsen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

A Lamarca and J Barriuso are part-funded by SEOM (Spanish Society of Medical Oncology) Translational Fellowship Grants.