Optimizing Somatostatin Analog Use in Well or Moderately Differentiated Gastroenteropancreatic Neuroendocrine Tumors

Somatostatin analogues, aiming to control tumor secretion or growth, constitute the most attractive therapeutic option for patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The objective of this article is to provide a comprehensive review of the current state-of-the-art knowledge gaps and potential opportunities for future development and optimization of this therapeutic modality.

A contextualized systematic review with a narrative component was conducted using PubMed, The Cochrane Library, EMBASE, and Google Scholar. Titles were screened, and non-English, duplicate, or irrelevant entries were excluded. Selection criteria for articles included the following: publication in English between 1995 and 2016, patients with GEP-NETs, analysis of efficacy, safety, practical management considerations, predictive factors, and/or strategies for overcoming resistance, concerning somatostatin analogs.

Ninety-seven studies out of 2771 screened publications met the inclusion criteria (16 randomized clinical trials, 27 phase II trials, 3 phase I trials, 3 subgroup analyses of clinical trials, 1 open-label extension of a randomized trial, 1 phase IV trial, 32 observational studies, and 14 basic research articles). The nature and scope of literature was diverse with most articles dedicated to drug efficacy or indications of use (n = 49), pharmacological issues (n = 8), assessment or predictors of response (n = 4), practical management (n = 11), combination therapy or other means to overcome resistance (n = 19), receptors and signaling pathways (n = 3), and subgroup analyses (n = 3).

In this appraisal, we have found some practical aspects that can help to the optimization of somatostatin analog (SSA) therapy in patients with well-differentiated GEP-NETs. We have also identified areas of uncertainty in an effort to guide clinical research in the coming years.