title: Sequential Everolimus and Sunitinib Treatment in Pancreatic Metastatic Well-Differentiated Neuroendocrine Tumours Resistant to Prior Treatments.
abstract: OBJECTIVE
  Alternating treatment with sunitinib and everolimus has been shown to be efficacious in renal cell carcinoma. However, no data currently exist for the role of alternate sequence administration of these agents in well-differentiated pancreatic neuroendocrine tumours (pNETs).
  
  
  METHODS
  Thirty-one patients were administered one compound and upon progression were switched to the other. All patients had grade 1 or 2 tumours and stage IV disease with similar metastatic load. The primary end point included estimation of the median overall progression-free survival (mPFS) along with each drug's mPFS as a first-line (mPFS1) and a second-line treatment (mPFS2); tolerability and serious adverse events were also evaluated. Secondary end points included overall survival (OS), 2-year mortality rate, and incidence of disease progression.
  
  
  RESULTS
  Overall, mPFS did not differ between the everolimus to sunitinib group (36.5 months) and the sunitinib to everolimus group (31.6 months) with a hazard ratio of 0.94 ([95% CI, 0.45-1.97], p = 0.7). Although mPFS1 after first-line everolimus was longer (16.3 months) compared to sunitinib (9 months), this was not statistically significant (p = 0.15). Sequential second-line treatment showed no difference in the mPFS2 (p = 0.3). No difference in OS between the 2 groups was observed. Tolerability was better for everolimus compared to sunitinib.
  
  
  CONCLUSIONS
  Treatment with sequential molecular target agents was well tolerated and associated with similar overall mPFS in both schemes of administration. Larger prospective studies are required to investigate the long-term efficacy and sequence of administration of alternate therapy with molecular targeting agents in metastatic pNETs and their effect on OS.
authors.affiliation: Sector of Endocrinology, Department of Pathophysiology, National &amp; Kapodistrian University of Athens, Athens, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Angelousi
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kamp
authors.forename: Maria
authors.initials: M
authors.lastname: Kaltsatou
authors.forename: Dermot
authors.initials: D
authors.lastname: O'Toole
authors.forename: Gregory
authors.initials: G
authors.lastname: Kaltsas
authors.forename: Wouter
authors.initials: W
authors.lastname: de Herder
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000068338:Everolimus; D000077210:Sunitinib
keywords: Everolimus; Molecular agents; Neuroendocrine tumour; Pancreas; Sunitinib; Survival