PMID- 31357193
OWN - NLM
STAT- MEDLINE
DCOM- 20210215
LR  - 20210215
IS  - 1423-0194 (Electronic)
IS  - 0028-3835 (Print)
IS  - 0028-3835 (Linking)
VI  - 110
IP  - 5
DP  - 2020
TI  - A Phase II Study of Ibrutinib in Advanced Neuroendocrine Neoplasms.
PG  - 377-383
LID - 10.1159/000502383 [doi]
AB  - BACKGROUND: Ibrutinib is an orally administered inhibitor of Bruton's tyrosine 
      kinase (Btk). Preclinical data suggest that mast cells are recruited within 
      neuroendocrine neoplasms (NENs) where they stimulate angiogenesis and tumor 
      growth. Ibrutinib inhibits mast cell degranulation and has been associated with 
      regression of tumors in a mouse insulinoma model. METHODS: A prospective, phase 
      II trial evaluated patients with advanced gastrointestinal (GI)/lung NENs and 
      pancreatic NENs (pNENs) who had evidence of progression within 12 months of study 
      entry on at least one prior therapy. Patients received ibrutinib 560 mg daily 
      until unacceptable toxicity, progression of disease, or withdrawal of consent. 
      The primary endpoint was objective response rate. RESULTS: Twenty patients were 
      enrolled on protocol from November 2015 to December 2017 (15 advanced GI/lung 
      NENs and 5 pNENs). No patient reached an objective response. Median PFS was 3.0 
      months. A total of 44 drug-related adverse events (AEs) were captured as probably 
      or definitely associated with ibrutinib. Five patients experienced probably or 
      definitely related grade 3 AEs, and 1 patient experienced a probably related 
      grade 4 AE. Five patients discontinued treatment prior to radiographic 
      assessment. CONCLUSIONS: Ibrutinib does not show significant evidence of activity 
      in well-differentiated gastroenteropancreatic and lung NENs.
CI  - (c) 2019 S. Karger AG, Basel.
FAU - Al-Toubah, Taymeyah
AU  - Al-Toubah T
AD  - Department of GI Oncology, H. Lee Moffitt Cancer Center and Research Institute, 
      Tampa, Florida, USA.
FAU - Schell, Michael J
AU  - Schell MJ
AD  - Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, 
      Tampa, Florida, USA.
FAU - Cives, Mauro
AU  - Cives M
AD  - Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, 
      Italy.
FAU - Zhou, Jun-Min
AU  - Zhou JM
AD  - Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, 
      Tampa, Florida, USA.
FAU - Soares, Heloisa P
AU  - Soares HP
AD  - Department of Oncology, University of New Mexico, Albuquerque, New Mexico, USA.
FAU - Strosberg, Jonathan R
AU  - Strosberg JR
AD  - Department of GI Oncology, H. Lee Moffitt Cancer Center and Research Institute, 
      Tampa, Florida, USA, jonathan.strosberg@moffitt.org.
LA  - eng
GR  - P30 CA076292/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190730
PL  - Switzerland
TA  - Neuroendocrinology
JT  - Neuroendocrinology
JID - 0035665
RN  - 0 (Piperidines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 1X70OSD4VX (ibrutinib)
RN  - EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacology
MH  - Adult
MH  - Agammaglobulinaemia Tyrosine Kinase/*antagonists & inhibitors
MH  - Aged
MH  - Carcinoid Tumor/*drug therapy
MH  - Female
MH  - Gastrointestinal Neoplasms/*drug therapy
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Neuroendocrine Tumors/*drug therapy
MH  - Pancreatic Neoplasms/*drug therapy
MH  - Piperidines/administration & dosage/adverse effects/*pharmacology
MH  - Prospective Studies
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects/*pharmacology
MH  - Treatment Failure
PMC - PMC7771542
MID - NIHMS1653134
OTO - NOTNLM
OT  - Carcinoid tumor
OT  - Ibrutinib
OT  - Neuroendocrine neoplasm
OT  - Pancreatic neuroendocrine tumor
COIS- Disclosure Statement Dr. Jonathan R. Strosberg has consulted for Novartis and has 
      received honoraria from Ipsen and Lexicon. Dr. Heloisa P. Soares has received 
      honoraria from Novartis, Ipsen, and Lexicon. None of the other authors declares a 
      personal or financial conflict of interest which could affect the outcome of this 
      study.
EDAT- 2019/07/30 06:00
MHDA- 2021/02/16 06:00
PMCR- 2021/01/01
CRDT- 2019/07/30 06:00
PHST- 2019/05/06 00:00 [received]
PHST- 2019/07/29 00:00 [accepted]
PHST- 2019/07/30 06:00 [pubmed]
PHST- 2021/02/16 06:00 [medline]
PHST- 2019/07/30 06:00 [entrez]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 000502383 [pii]
AID - 10.1159/000502383 [doi]
PST - ppublish
SO  - Neuroendocrinology. 2020;110(5):377-383. doi: 10.1159/000502383. Epub 2019 Jul 
      30.