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)

Abstract

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
• Status: Published
• Refereed: Yes
• 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: 0923-7534
• 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