Conko-006: a Randomized Double-Blinded Phase Iib-Study of Adjuvant Therapy with Gemcitabine + Sorafenib/Placebo for Patients with R1-Resection of Pancreatic Cancer

Abstract

Aim: Even after successful curatively intended surgery, up to 90% of patients (pts) with pancreatic cancer suffer a relapse. Adjuvant chemotherapy with gemcitabine (gem) or 5‐FU/folinic acid for 6 months (mo) significantly delays recurrence of disease, improves survival and increases the rate of cure in R0 and R1 patients. Based on these results, CONKO‐006 was designed for pts after R1 resection to analyse the benefit of a prolonged postoperative therapy with 12 instead of 6 months and to evaluate the safety and efficacy of the combination of gem (1000mg/m2 i.v. day 1,8,15, q29) and sorafenib (200 mg p.o. bid, day 1‐28, q29) or placebo planned for 12 cycles. Methods: In a randomized, double‐blinded placebo‐controlled multi‐center design, the study was planned based on the relapse rate to detect an improvement of disease‐free‐survival (DFS) from 42% to 60% after 18 mo. Secondary objectives were DFS at 12 and 24 mo, overall survival (OS) and treatment safety. Results: Between 02/2008 and 09/2013, 127 patients were included. Excluding 5 ineligible pts, 57 pts were randomised to SorGem and 65 to Gem. Pts characteristics are well balanced (SorGem/Gem) with median age (63/63y), tumor status (T3 + T4 97/97%), nodal status (N pos: 86/85%). Up to July 15th 111 events (91%) had occurred. Analysis shows no difference in median DFS [SorGem: 9.6 months (m), Gem: 10.7 m, p= 0.89] or OS [SorGem: 17.6 m, Gem: 15.6 m, p= 0.90]. Grade 3/4 toxicities per pt were: diarrhea (SorGem: 6%; Gem: 1%), fatigue (SorGem: 2%; Gem: 0%), neutropenia (SorGem: 7%; Gem: 16%), thrombocytopenia (SorGem: 4%; Gem: 1%), elevated GGT (SorGem: 8%; Gem: 5%), hypertension (SorGem: 2%; Gem: 0%), hand‐foot‐syndrome (SorGem: 3%; Gem: 0%). There was no relevant difference in median treatment duration: SorGem 27 weeks (range 1‐51); Gem 27 weeks (2‐62). Conclusions: CONKO‐006 is the largest randomized clinical trial exclusively for R1 resected pancreatic cancer patients so far. The combination therapy of Gemcitabine with the multityrosinkinase‐inhibitor Sorafenib for 12 months can not improve DFS or OS in this high‐risk cancer cohort. Disclosure: M. Sinn, H. Riess, U. Pelzer, J. Stieler, J.K. Striefler, M. Bahra, B. Dörken and H. Oettle: CONKO‐006 was supported in part by a grant from Bayer Vital AG.All other authors have declared no conflicts of interest.