Efficacy and Safety of Everolimus plus Somatostatin Analogues in Patients with Neuroendocrine Tumors

Everolimus, an oral mammalian target of rapamycin(mTOR) inhibitor, which acts upstream of the phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) signaling pathway to downregulate cellular metabolism, growth, proliferation, and angiogenesis, has been shown to significantly prolong the progression-free survival of patients with advanced neuroendocrine tumors. Somatostatin analogues (SSAs) such as octreotide, lanreotide, and pasireotide, have been widely used for symptom control and antiproliferative effects in metastatic or unresectable neuroendocrine tumors. Both everolimus and SSAs have demonstrated antitumor effects in randomized controlled trials (RCTs) involving selected patients with neuroendocrine tumors, but the efficacy and safety of their combined use require further investigation. In this systematic review, we summarize the published studies that have investigated the use of everolimus and SSAs to provide a comprehensive understanding of their combined effects and better guidance for the treatment of neuroendocrine tumors.