O-0001 - Phase 2 double-blind, placebo–controlled trial of dasatinib added to gemcitabine for subjects with locally-advanced pancreatic cancer (LAPC)

Date 25 June 2014
Event World GI 2014
Session Cancer of the pancreas and bile ducts
Topics Anti-Cancer Agents & Biologic Therapy
Pancreatic Cancer
Presenter J. Evans
Citation Annals of Oncology (2014) 25 (suppl_2): ii105-ii117. 10.1093/annonc/mdu193
Authors J. Evans1, M.J. Moore2, E. Rock3, L. Strauss4, P. ODwyer5
  • 1University of Glasgow, Glasgow/UK
  • 2Princess Margaret Hospital, Toronto/CA
  • 3Otsuka Pharmaceutical Development and Commercialization, Inc., Rockville/US
  • 4Bristol-Myers Squibb Pharmaceuticals Ltd., Wallingford/US
  • 5University of Pennsylvania, Philadelphia/US

Abstract

Introduction

Pancreatic adenocarcinoma (PDAC) remains an unmet medical need causing ∼ 200,000 deaths / year globally [Bilimoria KY, Cancer 2007; 110:738-44]. Gemcitabine (GEM) remains an acceptable standard of care [NCCN guidelines V 1 2014]. The oral tyrosine kinase inhibitor dasatinib (Das) inhibits SRC family members at nanomolar concentrations [Sprycel® (dasatinib) PI BMS], as well as tumor cell invasion and metastasis in a genetically engineered mouse PDAC model [Morton JP, Gastroenterology2010;139:292-303].

Methods

202 pts were randomized, 100 to G-Das and 102 to G-Plc. Regional enrollment: Western Europe (81), Central / Eastern Europe (59), North America (46), Australia (16). Treatment groups were balanced with, 51% male; median age 65 years (range 37-87); 38% and 61% ECOG PS 0 and 1, respectively; 94% Caucasian. Median tumor size was 41mm; 71% Stage3; 16% had nodal involvement; tumor locations were 75% head, 28% body & 8% tail. RT was intended in ∼50% of pts and administered to ∼18%.

Results

There was no PFS or OS difference between treatment groups. Median PFS and OS were 166 and 375 days for G-Das versus 167 and 393 days for G-Plc. Response rates were similar between groups. Treatment emergent adverse events (TEAE) occurred in 99% and 98% of G-Das and G-Plc pts, respectively. More G-Das pts reported ≥ Grade 3 AEs (87% vs. 63%), including cytopenias, liver abnormalities, pleural effusions, infections, pain, and fatigue. There was no evidence of increased deaths due to AEs.

Conclusion

In LAPC, OS and PFS are not improved when Das is added to GEM. G-Das is slightly more toxic.