title: Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives.
abstract: OBJECTIVE
  Everolimus has been shown to be effective for advanced pancreatic neuroendocrine tumours (pNETs), but its positioning in the therapeutic algorithm for pNETs is matter of debate.
  
  
  METHODS
  With the aim to shed light on this point, we performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies, and the recommendations of international guidelines. In addition, we performed an extensive search on the Clinical Trial Registries databases worldwide, to gather information on the ongoing clinical trials related to this specific topic.
  
  
  RESULTS
  We identified eight retrospective published studies, two prospective published studies, and five registered clinical trials. Moreover, we analyzed the content of four widespread international guidelines.
  
  
  CONCLUSIONS
  Our critical review confirms the lack of high-quality data to recommend everolimus as the first line therapy for pNETs. The ongoing clinical trials reported in this review will hopefully help clinicians, in the near future, to better evaluate the role of everolimus as the first line therapy for pNETs. However, at the moment, there is already enough evidence to recommend everolimus as the first line therapy for patients with symptomatic malignant unresectable insulin-secreting pNETs, to control the endocrine syndrome regardless of tumour growth.
authors.affiliation: Oncological Endocrinology Unit, Department of Medical Sciences, University of Turin, AOU Città della Salute e della Scienza di Torino, Via Genova 3, 10126, Turin, Italy. mgallo4@cittadellasalute.to.it.
authors.forename: Marco
authors.identifier: http://orcid.org/0000-0001-7166-0848
authors.initials: M
authors.lastname: Gallo
authors.affiliation: Endocrinology Unit, Garibaldi Nesima Medical Center, Catania, Italy.
authors.forename: Pasqualino
authors.initials: P
authors.lastname: Malandrino
authors.affiliation: Neuroendocrine Tumours Unit, Department of Clinical and Experimental Medicine, University of Sassari, AOU Sassari, Sassari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fanciulli
authors.affiliation: Endocrinology Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rota
authors.affiliation: Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, Naples, Italy.
authors.forename: Antongiulio
authors.initials: A
authors.lastname: Faggiano
authors.affiliation: Department of Clinical Medicine and Surgery, University "Federico II", Naples, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068338:Everolimus / Q000627:therapeutic use*; D006801:Humans; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus
keywords: Everolimus; Neuroendocrine tumours; Therapy; mTOR inhibitors