LBA18 - CONKO-006: A randomized double-blinded phase IIb-study of adjuvant therapy with gemcitabine + sorafenib/placebo for patients with R1-resection of p...

Date 28 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, non-colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Pancreatic Cancer
Presenter Marianne Sinn
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors M. Sinn1, T. Liersch2, K. Gellert3, H. Riess4, P. Stübs5, D.T. Waldschmidt6, U. Pelzer1, J. Stieler1, J.K. Striefler1, M. Bahra7, B. Dörken1, H. Oettle1
  • 1Medical Oncology, Charité-Universitätsmedizin Berlin, 13353 - Berlin/DE
  • 2University Of Göttingen, Department Of General And Visceral Surgery, University Göttingen, Göttingen/DE
  • 3General And Visceral Surgery, Sana Klinikum LIchtenberg, Berlin/DE
  • 4Medical Oncologcy, Charité-Universitätsmedizin Berlin, 13353 - Berlin/DE
  • 5Department Of General, Visceral And Vascular Surgery, Otto-von-Guericke University Magdeburg, Magdeburg/DE
  • 6Department Of Gastroenterology And Hepatology, University Köln, Köln/DE
  • 7Department Of General, Visceral And Transplantation Surgery, Charité-Universitätsmedizin Berlin, 13353 - Berlin/DE

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.