Impact of everolimus on Japanese patients with advanced pancreatic neuroendocrine neoplasms

J Hepatobiliary Pancreat Sci. 2017 Feb;24(2):95-102. doi: 10.1002/jhbp.418.


Background: Although everolimus has become a key therapeutic agent in patients with advanced pancreatic neuroendocrine neoplasms (PNEN), its efficacy and safety in clinical practice remains unclear.

Methods: Forty-seven patients with advanced PNEN treated with everolimus were reviewed retrospectively. To evaluate the safety of everolimus as a long-term treatment, the patients were divided into two groups according to treatment duration: group A, ≤1 year (n = 21); group B, >1 year (n = 26).

Results: Among 42 patients with pancreatic neuroendocrine tumors (PNET), the median progression-free survival, overall survival, and objective response rate were 27.5 months, 60.8 months, and 19.0%, respectively. Two patients with pancreatic neuroendocrine carcinomas (PNEC) with lower Ki-67 index and well-differentiated tumors showed favorable responses. More patients in group A discontinued everolimus owing to adverse drug reactions (ADRs) than in group B. The median relative dose intensity was significantly lower in group B than group A (P = 0.045), whereas the drug interruption rate was significantly higher in group B than group A (P < 0.001).

Conclusions: Everolimus showed significant clinical benefit in Japanese patients with advanced PNEN. Prevention of severe ADRs by appropriate dose reduction and interruption is necessary for a long-term continuation of everolimus.

Keywords: Everolimus; Pancreatic neuroendocrine carcinomas; Pancreatic neuroendocrine neoplasms; Pancreatic neuroendocrine tumors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Everolimus / therapeutic use*
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / drug therapy*
  • Pancreatic Neoplasms / drug therapy*
  • Retrospective Studies
  • Treatment Outcome


  • Antineoplastic Agents
  • Everolimus