Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer

Evans, T.R.J. et al. (2017) Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer. Annals of Oncology, 28(2), pp. 354-361. (doi: 10.1093/annonc/mdw607) (PMID:27998964)

116871.pdf - Accepted Version



Background: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in 2 of 8 patients with gemcitabine-refractory PDAC. Patients and methods: This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC. Patients received gemcitabine 1,000 mg/m2 (30- minute IV infusion) on days 1, 8, 15 of a 28-day cycle combined with either 100 mg oral dasatinib or placebo tablets daily. The primary objective was overall survival (OS), with safety and progression-free survival (PFS) as secondary objectives. Exploratory endpoints included overall response rate, freedom from distant metastasis, pain and fatigue progression and response rate, and CA19-9 response rate. Results: There was no statistically significant difference in OS between the 2 treatment groups (HR = 1.16; 95% confidence interval [CI]: 0.81–1.65; p=0.5656). Secondary and exploratory endpoint analyses also showed no statistically significant differences. The burden of toxicity was higher on the dasatinib arm. Conclusions: Dasatinib failed to show increased OS or PFS in patients with locally advanced PDAC. Alternative combinations or trial designs may show a role for src inhibition in PDAC treatment.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Evans, Professor Jeff
Authors: Evans, T.R.J., Van Cutsem, E., Moore, M.J., Bazin, I.S., Rosemurgy, A., Bodoky, G., Deplanque, G., Harrison, M., Melichar, B., Pezet, D., Elekes, A., Rock, E., Lin, C., Strauss, L., and O'Dwyer, P.J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Annals of Oncology
Publisher:Oxford University Press
ISSN (Online):1569-8041
Published Online:19 December 2016
Copyright Holders:Copyright © 2016 Oxford University Press
First Published:First published in Annals of Oncology 28(2):354-361
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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