Efficacy and safety of everolimus and sunitinib in patients with gastroenteropancreatic neuroendocrine tumor

Cancer Chemother Pharmacol. 2017 Jan;79(1):139-146. doi: 10.1007/s00280-016-3215-3. Epub 2016 Dec 10.

Abstract

Purpose: Efficacy of targeted agents, such as everolimus and sunitinib, has been demonstrated in prospective trials on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Considering the heterogeneous clinicopathological characteristics of neuroendocrine tumors (NETs), evaluation of treatment outcomes in a real-world setting is necessary.

Methods: Clinical records of 44 patients with GEP-NET who were treated with everolimus or sunitinib between March 2007 and October 2014 were retrospectively reviewed. Considering the distinct characteristics of pancreatic NETs (pNETs) and non-pancreatic gastrointestinal NETs (GI-NETs), efficacy analysis was performed separately.

Results: Pancreas was the most common primary site (n = 28, 64%), followed by rectum (n = 10, 23%) and stomach (n = 3, 7%). Sunitinib and everolimus were administered in 27 (61%) and 17 (39%) patients, respectively. In patients with pNET, median progression-free survival (PFS) with everolimus and sunitinib was 16.6 months (95% CI 8.0-25.1) and 8.0 months (95% CI 0.0-17.4), respectively (p = 0.51). Among non-pancreatic GI-NET patients, median PFS with everolimus and sunitinib was 14.7 months (95% CI 2.4-27.0) and 1.7 months (95% CI 0.5-3.0), respectively (p = 0.001). Compared to patients treated with everolimus, tumor grade 3 (30 vs. 0%) and history of prior cytotoxic chemotherapy (70 vs. 50%) were more common in patients treated with sunitinib.

Conclusions: Both everolimus and sunitinib were effective in GEP-NET patients. Outcomes of everolimus therapy in GEP-NETs were consistent with those reported elsewhere. Poor efficacy of sunitinib in non-pancreatic GI-NETs may be attributable to the baseline characteristics associated with poor clinical outcomes.

Keywords: Everolimus; Gastroenteropancreatic; Neuroendocrine tumor; Sunitinib.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Disease-Free Survival
  • Everolimus / adverse effects
  • Everolimus / therapeutic use*
  • Female
  • Humans
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Intestinal Neoplasms / drug therapy*
  • Intestinal Neoplasms / mortality
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / mortality
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Retrospective Studies
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Sunitinib

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Everolimus
  • Sunitinib

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor