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Clinical Trial
. 2020;110(5):377-383.
doi: 10.1159/000502383. Epub 2019 Jul 30.

A Phase II Study of Ibrutinib in Advanced Neuroendocrine Neoplasms

Taymeyah Al-Toubah  1 , Michael J Schell  2 , Mauro Cives  3 , Jun-Min Zhou  2 , Heloisa P Soares  4 , Jonathan R Strosberg  5
Affiliations
Clinical Trial

A Phase II Study of Ibrutinib in Advanced Neuroendocrine Neoplasms

Taymeyah Al-Toubah et al. Neuroendocrinology. 2020.

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.

Keywords: Carcinoid tumor; Ibrutinib; Neuroendocrine neoplasm; Pancreatic neuroendocrine tumor.

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Conflict of interest statement

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.

Figures

Fig. 1.
Fig. 1.
Summary of prior therapies.
Fig. 2.
Fig. 2.
Best responses according to RECIST 1.1. PD, progressive disease.
Fig. 3.
Fig. 3.
Kaplan-Meier estimates of PFS. PFS, progression-free survival.
Fig. 4.
Fig. 4.
Kaplan-Meier estimates of OS. OS, overall survival.
See this image and copyright information in PMC

References

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