Phase III results of exatecan (DX-8951f) versus gemcitabine (Gem) in chemotherapy-naïve patients with advanced pancreatic cancer (APC)

4005 Background: Ensiv (Exatecan) is a novel hexacyclic, water-soluble, topoisomerase-1 inhibitor. Ensiv has single-agent and combination activity with Gem in APC (D'Adamo, et al. ProcASCO, 2001; O'Reilly, et al. ProcASCO, 2002). Methods: A multi-centre randomised phase III trial comparing Ensiv with gemcitabine in APC has been completed. Eligibility included KPS ≥ 60%; locally advanced or metastatic disease; no prior chemotherapy. Patients (pts) were randomised in a 1:1 ratio to Ensiv (0.5 mg/m2 daily x 5 q3w) or gemcitabine (1000 mg/m2 weekly x 7 then 1 week rest, then weekly x 3 q4w). Treatment continued until disease progression or intolerable toxicity. Primary endpoint was overall survival (OS). Study was powered to demonstrate a 50% increase in OS from 5.1 to 7.65 months. Analysis will be conducted based on 263 events (deaths) having occurred. An independent data safety monitoring board monitored the trial. Results: Altogether, an Intent To Treat (ITT) population of 339 pts (Ensiv 169, Gem 170) were randomised at 67 sites between July 2001 and Jan 2003. Of these 330 (165 Ensiv; 165 Gem) received treatment. Demographic factors were well balanced for age, sex, PS and disease extent. In the ITT population for Ensiv 139 pts died and 30 were censored (gem 137; 33) at data cut-off following the 263 event ocurrence as prescribed in the statistical analysis plan. Survival: Median Survival Times (MST) were Ensiv 151 days; Gem 197 days), 6-month Survival rates Ensiv 44.1%; Gem 51.1%, and 12-month Survival rates Ensiv 17.9%; Gem 22.1%. Response rates seen were: Ensiv 0CR, 1PR, 75 SD; Gem 3CR, 10PR, 78 SD. Median Time to Tumor Progression (TTP) was; Ensiv 85 days; Gem 132 days. Gem was superior to Ensiv in both weight loss and pain worsening ( weight loss; Ensiv 69 days vs Gem 114 days; pain VAS; 112 days vs 236 days; analgesic consumption increase; 69 days vs 114 days) as well as in QOL evaluation. Treatment emergent toxicities are tabulated below: Conclusions: Single agent Ensiv did not show the expected increase in survival or clinical benefit over gemcitabine in this study Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Daiichi Pharmaceuticals UK Ltd Daiichi Pharmaceuticals