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.

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.

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review.

BACKGROUND: Approximately 20% of patients with neuroendocrine tumours (NETs) develop carcinoid syndrome (CS), characterised by flushing and diarrhoea. Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion. Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs (GEP-NETs), other causes to consider include pancreatic enzyme insufficiency (PEI), bile acid malabsorption and small intestinal bacterial overgrowth. If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea, these treatments may be ineffective against the diarrhoea, risking detrimental effects to patient quality of life. AIM: To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs. METHODS: Electronic databases (MEDLINE, Embase and the Cochrane Library) were searched from inception to September 12, 2018 using terms for NETs and diarrhoea. Congresses, systematic literature review bibliographies and included articles were also hand-searched. Any study designs and publication types were eligible for inclusion if relevant data on a cause(s) of diarrhoea in patients with GEP-NETs were reported. Studies were screened by two independent reviewers at abstract and full-text stages. Framework synthesis was adapted to synthesise quantitative and qualitative data. The definition of qualitative data was expanded to include all textual data in any section of relevant publications. RESULTS: Forty-seven publications (44 studies) were included, comprising a variety of publication types, including observational studies, reviews, guidelines, case reports, interventional studies, and opinion pieces. Most reported on PEI on/after treatment with somatostatin analogs; 9.5%-84% of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI. Where reported, 14.3%-50.7% of patients received pancreatic enzyme replacement therapy. Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption (80%), small intestinal bacterial overgrowth (23.6%-62%), colitis (20%) and infection (7.1%). Diagnostic approaches included faecal elastase, breath tests, tauroselcholic (selenium-75) acid (SeHCAT) scan and stool culture, although evidence on the effectiveness or diagnostic accuracy of these approaches was limited. Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation. From the identified evidence, if diarrhoea is assumed to be CS diarrhoea, consequences include uncontrolled diarrhoea, malnutrition, and perceived ineffectiveness of CS treatment. Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team, including gastroenterologists. CONCLUSION: Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use. This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches, to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.