CONKO-001: Final results of the randomized, prospective, multicenter phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer (PC)

Abstract

LBA4504 Background: Prognosis of patients (pts) with PC is dismal, even after curatively intended resection. Whereas gemcitabine-based chemotherapy is standard in advanced PC, the role of adjuvant chemotherapy is still under discussion. Methods: CONKO-001, a prospective, open, multicenter, controlled phase 3 study was designed to evaluate the efficacy and toxicity of gemcitabine in PC pts after complete (R0 or R1) resection. After stratification for R0/R1, nodal tumour involvement and tumour stage pts were randomized to receive either gemcitabine (G) (1g/m2 d 1, 8 and 15 every 4 weeks) for 6 months or observation (O). Pts in the observation group received no specific anticancer treatment. Primary study endpoint was disease free survival (DFS), secondary endpoints included OS and toxicity. The study was powered to detect a significant difference in DFS with 90% probability at a significance level of .05 on all eligible patients. Results: Between July 1998 and December 2004 368 pts were randomized and 354 were eligible for intent-to-treat-analysis. As previously discribed in JAMA 2007 first results showed that postoperative G is well tolerated and significantly delays the development of recurrent disease after complete resection of PC. By December 1st 2007 303 events (85.6%) have occurred for DFS and 293 events (82.8%) for OS. The analyses confirm the significant improvement for G in median DFS [G:13.4 months (m), O: 6.9m, p< .001]. Estimated DFS at 3 and 5 years was 23.5% and 16.0% in the G group vs. 8.5% and 6.5% in the O group, respectively. Subgroup analyses demonstrate significant increased DFS for G in all subgroups of stratification. G significantly improves median OS [G:22.8m, O: 20.2m, p=.005]. Estimated survival at 3 and 5 years was 36.5% and 21.0% for G pts vs. 19.5% and 9.0% for O pts, respectively. Conclusion: Treatment with G for 6 months for pts after complete resection of PC significantly increases DFS and OS compared with O alone. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Bayer, Lilly Oncology, Merck, Novartis, Pfizer, Roche, sanofi-aventis