title: Everolimus in advanced pancreatic neuroendocrine tumors: the clinical experience.
abstract: The incidence of neuroendocrine tumors (NET) has increased dramatically in the past 30 years. This information has revitalized basic and clinical research into the molecular biology of NET and has resulted in the recent approval of new therapies for pancreatic NET (pNET), including the oral inhibitor of the mTOR everolimus. Everolimus significantly improved progression-free survival among patients with pNET in the phase III RADIANT-3 study. Here, we review the clinical studies showing the efficacy of everolimus in pNET and summarize the translational science from these studies. To understand the mechanisms of resistance and cause of treatment failure, we compared the type of progression events observed in the everolimus and placebo arms of the RADIANT-3 study. Comparison of the everolimus arm to the placebo arm indicated the fractions of progression events due to new metastasis only (21% vs. 22%), growth of preexisting lesions only (54% vs. 49%), and new metastasis along with growth of preexisting lesions (24% vs. 27%) were similar. These results suggest that although everolimus delays disease progression in patients with pNET, patients who experience disease progression while on everolimus do not appear to have a more aggressive metastatic phenotype than those whose disease progresses while on placebo.
authors: Departments of Gastrointestinal Medical Oncology and Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. jyao@mdanderson.org
authors: James C
authors: JC
authors: Yao
authors: Alexandria T
authors: AT
authors: Phan
authors: Valentine
authors: V
authors: Jehl
authors: Gaurav
authors: G
authors: Shah
authors: Funda
authors: F
authors: Meric-Bernstam
mesh_terms: D002986:Clinical Trials as Topic; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000401:mortality; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus