Systemic treatment for neuroendocrine neoplasms (NENs) has evolved over the years and has accelerated more recently owing to better understanding of NENs biology and updated classification of the disease. Somatostatin analogues (SSAs) have been the mainstay treatment for advanced neuroendocrine tumors (NETs) which express somatostatin receptors (SSTRs) [1]. This treatment offers both disease control and symptom management as it relates to hormonal secretion [1], [2], [3]. Beyond SSA, the armamentarium of treatments for NETs continues to expand. More recently in 2018, based on the results of the NETTER-1 trial, the FDA approved the peptide receptor radionuclide (PRRT) Lutetium-177 (Lu177) DOTATATE for the treatment of well-differentiated GEP-NETs [4]. Further, the mTOR inhibitor, everolimus, was approved for the treatment of non-functional well-differentiated GEP-NETs based on the RADIANT studies [5]. In terms of TKIs, the only FDA approved therapy is sunitinib for the treatment of well differentiated PNETs [6]. Lastly, based on the ECOG (Eastern Cooperative Oncology Group) E2211 study, capecitabine and temozolomide (CAPTEM) are effective therapy for the treatment of well-differentiated (grade 1 and 2) PNETs [7].

In this review article, we will focus on the role and updates of tyrosine kinase inhibitors (TKIs) as well as immunotherapy or immune check point inhibitors (ICIs) in the management of advanced NETs.