Renuka V Iyer1, Bhavana Konda2, Christos Fountzilas1, Sarbajit Mukherjee1, Dwight Owen2, Kristopher Attwood3, Chong Wang3, Orla Maguire4, Hans Minderman4, Sheryl-Ann Suffren2, Karen Hicks5, John Wilton6, Robert Bies6, Danielle Casucci5, Diane Reidy-Lagunes7, Manisha Shah2. 1. Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York. 2. Department of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio. 3. Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York. 4. Flow and Image Cytometry Shared Resource, Roswell Park Comprehensive Cancer Center, Buffalo, New York. 5. Department of Clinical Research Services, Roswell Park Comprehensive Cancer Center, Buffalo, New York. 6. Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York. 7. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Abstract
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.
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.
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