Systemic Therapy for Pancreatic Neuroendocrine Tumors

Patients with metastatic or advanced pancreatic neuroendocrine tumors (NETs) carry poorer prognoses relative to patients with other NETs due to bulkier and often, more proliferative baseline disease. Patients with these tumors also possess more approved treatment options relative to patients with other NETs, making therapeutic sequencing nuanced. As such, defining optimal therapeutic sequencing and developing more potent cytoreductive treatments for patients are significant areas of research need in the field. Herein this review, we discuss the current systemic therapy landscape, our approach to therapeutic sequencing in the clinic and ongoing studies seeking to define optimal sequencing of systemic therapies, and novel therapeutics in development, for patients with pancreatic NETs. We limit the scope of this latter topic to agents with preclinical or clinical rationale over the last 8 years to provide a contemporary view of the drug development landscape and focus primarily on new types of peptide receptor radionuclide therapy, anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors and anti-vascular endothelial growth receptor tyrosine kinase inhibitor plus immunotherapy combinations.