Taymeyah Al-Toubah1, Michael J Schell2, Mauro Cives3, Jun-Min Zhou2, Heloisa P Soares4, Jonathan R Strosberg5. 1. Department of GI Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. 2. Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. 3. Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy. 4. Department of Oncology, University of New Mexico, Albuquerque, New Mexico, USA. 5. Department of GI Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA, jonathan.strosberg@moffitt.org.
Abstract
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.
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 mouseinsulinoma 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.
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