A Review of Systemic and Liver-Directed Therapies for Metastatic Neuroendocrine Tumors of the Gastroenteropancreatic Tract

Background: Treatment options for metastatic gastroenteropancreatic neuroendocrine tumors (NETs) have evolved in recent years. The somatostatin analogs octreotide and lanreotide have long been used for management of symptoms such as flushing and diarrhea associated with hormonally active NETs. New evidence demonstrates that these agents can also inhibit tumor growth. Other novel agents targeting the VEGF and mTOR pathways have recently been investigated in multicenter phase III studies. Methods: The authors review the recent literature on treatments for metastatic gastroenteropancreatic NETs and summarize new therapeutic developments. Results: Novel agents targeting somatostatin receptors and the VEGF and mTOR pathways are capable of significantly prolonging progression-free survival in certain NET subtypes. New temozolomide-based chemotherapy regimens have demonstrated considerable activity in pancreatic NETs. Liver-targeted therapies, including surgical resection, radiofrequency ablation, and hepatic artery embolization, are effective options for patients whose metastases are predominantly confined to the liver. Embolization of Y-90-embedded spheres (radioembolization) represents a novel approach to managing liver metastases. Conclusions: Treatment options are expanding rapidly for patients with metastatic gastroenteropancreatic NETs, driven largely by randomized, collaborative clinical trials. Future clinical trials should compare the efficacy of emerging therapies and evaluate combination vs sequential approaches.