Prognostic impact of the cumulative dose and dose intensity of everolimus in patients with pancreatic neuroendocrine tumors

Cancer Med. 2017 Jul;6(7):1493-1499. doi: 10.1002/cam4.1028. Epub 2017 May 25.


The aim of this work is to assess if cumulative dose (CD) and dose intensity (DI) of everolimus may affect survival of advanced pancreatic neuroendocrine tumors (PNETs) patients. One hundred and sixteen patients (62 males and 54 females, median age 55 years) with advanced PNETs were treated with everolimus for ≥3 months. According to a Receiver operating characteristics (ROC) analysis, patients were stratified into two groups, with CD ≤ 3000 mg (Group A; n = 68) and CD > 3000 mg (Group B; n = 48). The response rate and toxicity were comparable in the two groups. However, patients in group A experienced more dose modifications than patients in group B. Median OS was 24 months in Group A while in Group B it was not reached (HR: 26.9; 95% CI: 11.0-76.7; P < 0.0001). Patients who maintained a DI higher than 9 mg/day experienced a significantly longer OS and experienced a trend to higher response rate. Overall, our study results showed that both CD and DI of everolimus play a prognostic role for patients with advanced PNETs treated with everolimus. This should prompt efforts to continue everolimus administration in responsive patients up to at least 3000 mg despite delays or temporary interruptions.

Keywords: Everolimus; mTOR inhibitor; pancreatic neuroendocrine tumors; targeted therapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Combined Modality Therapy
  • Everolimus / administration & dosage*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Grading
  • Neoplasm Staging
  • Neuroendocrine Tumors / diagnosis
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / mortality*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality*
  • Prognosis
  • Protein Kinase Inhibitors / administration & dosage
  • ROC Curve
  • Treatment Outcome
  • Young Adult


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Everolimus