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

Jeffrey T.R.J. Evans, E. Van Cutsem, M. J. Moore, I. S. Bazin, A. Rosemurgy, G. Bodoky, G. Deplanque, M. Harrison, B. Melichar, D. Pezet, A. Elekes, E. Rock, C. Lin, L. Strauss, P. J. O'Dwyer

Research output: Article

25 Citations (Scopus)

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 two of eight 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 1000 mg/m2 (30-min 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 two 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 in 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.

Original languageEnglish
Pages (from-to)354-361
Number of pages8
JournalAnnals of Oncology
Volume28
Issue number2
DOIs
Publication statusPublished - 2017

ASJC Scopus subject areas

  • Hematology
  • Oncology

Fingerprint Dive into the research topics of 'Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer'. Together they form a unique fingerprint.

  • Cite this

    Evans, J. 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., & O'Dwyer, P. J. (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), 354-361. https://doi.org/10.1093/annonc/mdw607