Multicenter phase 2 trial of nintedanib in advanced nonpancreatic neuroendocrine tumors

Renuka V. Iyer, Bhavana Konda, Christos Fountzilas, Sarbajit Mukherjee, Dwight Owen, Kristopher Attwood, Chong Wang, Sheryl Ann Suffren, Karen Hicks, John Wilton, Robert Bies, Danielle Casucci, Diane Reidy-Lagunes, Manisha Shah

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Pages (from-to)3689-3697
Number of pages9
Issue number16
StatePublished - Aug 15 2020


  • angiogenesis
  • neuroendocrine tumors
  • nintedanib
  • serotonin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Iyer, R. V., Konda, B., Fountzilas, C., Mukherjee, S., Owen, D., Attwood, K., Wang, C., Suffren, S. A., Hicks, K., Wilton, J., Bies, R., Casucci, D., Reidy-Lagunes, D., & Shah, M. (2020). Multicenter phase 2 trial of nintedanib in advanced nonpancreatic neuroendocrine tumors. Cancer, 126(16), 3689-3697.