Multicenter phase 2 trial of nintedanib in advanced nonpancreatic neuroendocrine tumors

Cancer. 2020 Aug 15;126(16):3689-3697. doi: 10.1002/cncr.32994. Epub 2020 Jun 11.


Background: Antiangiogenic-targeting agents have low response rates in patients with nonpancreatic neuroendocrine tumors (NETs). Nintedanib is an oral antiangiogenic agent that has inhibitory effects on the fibroblast growth factor receptor, which is highly expressed in NETs. The authors hypothesized that nintedanib would be active in patients with nonpancreatic NETs.

Methods: Patients with advanced, grade 1 or 2, nonpancreatic NETs who were receiving a stable dose of somatostatin analogue were enrolled. Nintedanib was administered at a dose of 200 mg twice daily in 28-day cycles. The primary endpoint was progression-free survival (PFS) at 16 weeks.

Results: Thirty-two patients were enrolled, and 30 were evaluable for the primary outcome. Most had radiographic disease progression within 12 months before enrollment. The 16-week PFS rate was 83%, and the median PFS and overall survival were 11.0 months and 32.7 months, respectively. Nintedanib was well tolerated and delayed deterioration in quality of life. The baseline serotonin level had a strong, positive correlation with activated but exhausted T cells.

Conclusions: Nintedanib is active in nonpancreatic NETs. The immunosuppressive effect of serotonin should be targeted in future clinical trials.

Keywords: angiogenesis; neuroendocrine tumors; nintedanib; serotonin.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Disease Progression
  • Female
  • Humans
  • Indoles / administration & dosage*
  • Indoles / adverse effects
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Neuroendocrine Tumors / drug therapy*
  • Progression-Free Survival
  • Somatostatin / administration & dosage
  • Somatostatin / adverse effects
  • Treatment Outcome


  • Angiogenesis Inhibitors
  • Indoles
  • Somatostatin
  • nintedanib