Multicenter phase 2 trial of nintedanib in advanced nonpancreatic neuroendocrine tumors.
Aged
Angiogenesis Inhibitors
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Disease Progression
Female
Humans
Indoles
/ administration & dosage
Male
Middle Aged
Neoplasm Staging
Neovascularization, Pathologic
/ drug therapy
Neuroendocrine Tumors
/ drug therapy
Progression-Free Survival
Somatostatin
/ administration & dosage
Treatment Outcome
angiogenesis
neuroendocrine tumors
nintedanib
serotonin
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
15 08 2020
15 08 2020
Historique:
received:
14
04
2020
accepted:
02
05
2020
pubmed:
12
6
2020
medline:
19
5
2021
entrez:
12
6
2020
Statut:
ppublish
Résumé
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. 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. 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. Nintedanib is active in nonpancreatic NETs. The immunosuppressive effect of serotonin should be targeted in future clinical trials.
Sections du résumé
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.
Identifiants
pubmed: 32525561
doi: 10.1002/cncr.32994
pmc: PMC8396074
mid: NIHMS1717491
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Indoles
0
Somatostatin
51110-01-1
nintedanib
G6HRD2P839
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3689-3697Subventions
Organisme : Boehringer Ingelheim Pharmaceuticals
Organisme : NCI NIH HHS
ID : R50 CA211108
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P30CA016056
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016056
Pays : United States
Organisme : National Comprehensive Cancer Network
Informations de copyright
© 2020 American Cancer Society.
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