Systemic Therapy in Incurable Gastroenteropancreatic Neuroendocrine Tumours: A Clinical Practice Guideline
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abstract
Purpose: The purpose of the present review was to determine which antineoplastic systemic therapy is most effective in improving clinical outcomes for patients with incurable gastroenteropancreatic neuroendocrine tumours (NETS). Methods: A systematic search (2008–2016) of the literature in the medline and embase databases and the Cochrane Database of Systematic Reviews was conducted; abstracts from the American Society of Clinical Oncology, the American Society of Clinical Oncology Gastrointestinal Cancers Symposium, the European Society for Medical Oncology, the European Cancer Congress, the European Neuroendocrine Tumor Society, and the North American Neuroendocrine Tumor Society were reviewed. Draft recommendations were created, and a comprehensive review process was undertaken. Outcomes—including progression-free survival (PFS), overall survival, objective response rate, adverse events, and quality of life—were extracted from each of the studies. Results: Eleven randomized controlled trials (RCTS), sixteen nonrandomized prospective studies, and thirteen retrospective studies met the inclusion criteria. Conclusions: Patients with well- or moderately-differentiated pancreatic NETS (PNETS) should receive targeted therapy (that is, everolimus or sunitinib), and patients with non-PNETS should be offered either targeted therapy (that is, everolimus) or somatostatin analogues (SSAS—that is, octreotide long-acting release or lanreotide). Evidence from two phase iii trials demonstrated a significant PFS benefit for patients with PNETS. For patients with non-PNETS, the evidence comes from subgroup analyses of RCTS, as well as from a planned interim analysis. Although the evidence has limitations, the rarity of the disease, coupled with the difficulty of conducting methodologically sound trials in the affected population, means that treatment decisions have to make use of the best available evidence. Because of insufficient evidence for both PNETS and non-PNETS, no evidence-based recommendation can be made for or against other types of targeted therapy, other SSAS, chemotherapy, or combination therapy.
