Abstract
Background
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.
Method
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.
Results
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).
Conclusion
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.
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Abbreviations
- CLARINET :
-
Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors trial
- NETTER-1 :
-
phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial
- PROMID :
-
Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors
- RADIANT-3 :
-
RAD001 in Advanced Neuroendocrine Tumors, third trial
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This project was funded in part by a restricted educational grant from Ipsen Pharma S.A. This group did not intervene in the design, analysis, interpretation of research, writing of the manuscript, approval, nor in the decision to submit the manuscript.
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Alberto Carmona-Bayonas declares that he has no conflict of interest.
Paula Jiménez-Fonseca declares that she has no conflict of interest.
Ana Custodio declares that she has no conflict of interest.
Enrique Grande declares that he has no conflict of interest.
Jaume Capdevila has served as a guest speaker for Ipsen Pharma S.A., Novartis, Pfizer, and Advanced Accelerator Applications.
Carlos López has received compensation for service as a consultant as well as research funding through grants from Ipsen Pharma S.A., Novartis, Pfizer, and Eisai.
Alex Teule declares that he has no conflict of interest.
Rocío Garcia-Carbonero has received compensation for service as a consultant as well as research funding through grants and non-financial support from Ipsen Pharma S.A. and Novartis.
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Carmona-Bayonas, A., Jiménez-Fonseca, P., Custodio, A. et al. Optimizing Somatostatin Analog Use in Well or Moderately Differentiated Gastroenteropancreatic Neuroendocrine Tumors. Curr Oncol Rep 19, 72 (2017). https://doi.org/10.1007/s11912-017-0633-2
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DOI: https://doi.org/10.1007/s11912-017-0633-2