Clinical outcomes of everolimus in patients with advanced, nonfunctioning pancreatic neuroendocrine tumors: a multicenter study in Korea

Cancer Chemother Pharmacol. 2017 Oct;80(4):799-805. doi: 10.1007/s00280-017-3421-7. Epub 2017 Sep 7.


Purpose: Everolimus is a standard treatment option for advanced pancreatic neuroendocrine tumors (pNETs). This multicenter study evaluated the efficacy and safety of everolimus in low and intermediate grade advanced pNETs.

Methods: Tumors were graded according to the World Health Organization 2010 classification system. Patients with low or intermediate grade pNETs who received everolimus as first- or second-line chemotherapy between 2002 and 2014 were included.

Results: A total of 40 patients with metastatic or recurrent pNETs were included in this study. The median age was 54.5 years (range 19-83 years). Twelve patients (30%) experienced recurrence. There were 11 patients (27.5%) with low grade pNETs and 29 (72.5%) with intermediate. Everolimus was administered as first-line therapy in 30 patients (75%) and as second-line therapy in 10 patients (25%). The median progression-free survival (PFS) of patients with low and intermediate grade pNETs was significantly different (median not reached vs. 11 months, P = 0.015). On multivariate analysis, tumor grade (intermediate grade; HR 6.52, 95% CI 1.31-32.27, P = 0.022) was the only independent prognostic factor for PFS in pNETs. The most common adverse events were stomatitis, skin rash, and anemia.

Conclusions: World Health Organization 2010 grade is the most important determinant for PFS in patients undergoing everolimus treatment for pNETs with an acceptable incidence of adverse events.

Keywords: Everolimus; Pancreatic neuroendocrine tumor; Prognosis; Tumor grade; World Health Organization classification.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia / chemically induced
  • Anemia / epidemiology
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Disease-Free Survival
  • Everolimus / adverse effects
  • Everolimus / therapeutic use*
  • Exanthema / chemically induced
  • Exanthema / epidemiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Republic of Korea
  • Retrospective Studies
  • Stomatitis / chemically induced
  • Stomatitis / epidemiology
  • Treatment Outcome
  • Young Adult


  • Antineoplastic Agents
  • Everolimus

Supplementary concepts

  • Non functioning pancreatic endocrine tumor