Systemic Treatment Options for Carcinoid Syndrome: A Systematic Review

Background: Carcinoid syndrome symptoms significantly reduce quality of life in patients with neuroendocrine tumors. Evidence supporting the use of somatostatin analogues in carcinoid syndrome symptom control dates back 30 years. The introduction of new treatment options for carcinoid syndrome, such as telotristat ethyl in 2017, highlights the need for a review of high-level evidence of new and established systemic treatments. Objective: To examine the efficacy and safety of systemic treatment options for patients with carcinoid syndrome. Method: A systematic review of English language articles was conducted using PubMed, EMBASE, and the Cochrane Controlled Trials Register using the search terms carcinoid syndrome, clinical trial, clinical study, and prospective study. Additional studies were identified by searching abstracts from oncology or neuroendocrine tumor congresses during the previous year. Prospective, interventional, phase II or III clinical trials or pivotal trials leading to drug approval were included. Studies were required to have >85% of patients with carcinoid syndrome; secondary publications were excluded. Results: The search identified 233 unique records, of which 12 trials met the criteria for inclusion. Interventions assessed in these trials included short-acting and long-acting octreotide, lanreotide prolonged-release and autogel/depot, short-acting and long-acting pasireotide, telotristat ethyl, everolimus, and peptide receptor radionuclide therapy. Somatostatin analogues provided substantial symptom relief for patients with carcinoid syndrome. For refractory symptoms, an increased dose of somatostatin analogue or addition of telotristat ethyl were valuable options. Interventions were generally well tolerated, with few serious treatment-related adverse events. Conclusions: By critically evaluating high-level evidence in a rigorous manner, this review highlights the general lack of consensus regarding what defines symptom control in studies of carcinoid syndrome and the need for standardized treatment guidelines for this disease. More prospective trials of treatments for carcinoid syndrome are warranted to assist oncologists with optimizing treatment selection and sequencing in this patient population.