Systemic therapies for advanced gastroenteropancreatic neuroendocrine tumors.

INTRODUCTION: Neuroendocrine tumors are a heterogeneous group of malignancies, characterised by production of hormones and vasoactive peptides. The incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NET) is rising, and they have the highest prevalence amongst upper gastro-intestinal tumors. Diagnosis remains challenging due to wide variations in presentation and slow onset of symptoms. A multi-disciplinary approach is vital in appropriately managing the diverse spectrum of GEP-NET. Areas covered: Investigations in GEP-NET and biomarkers are described. Moreover, all available therapeutic options for GEP-NET including surgery, somatostatin analogues, targeted agents, Peptide Receptor Radionuclide Therapy and chemotherapy are also discussed. Expert commentary: The landscape of management has changed significantly in the last decade as a result of many practice-changing clinical trials. Long- acting somatostatin analogues are used not only for symptom control but also for their anti-proliferative effect. Targeted agents, such as everolimus and sunitinib, have improved PFS in GEP-NET. The recently presented NETTER-1 trial confirms the place of peptide receptor radionuclide treatment (PRRT) in treating NET. While chemotherapy remained an important option for high grade tumors. Despite promising results from recent trials, challenges include establishing the optimal sequencing of therapies to optimize outcome and preserve the quality of life.