O-0024 - Prognostic value of KRAS mutations in stage III colon cancer: post-hoc analyses of the PETACC8 phase III trial

Date 27 June 2014
Event World GI 2014
Session Presentation of selected abstracts
Topics Colon Cancer
Translational Research
Presenter Julien Taieb
Citation Annals of Oncology (2014) 25 (suppl_2): ii105-ii117. 10.1093/annonc/mdu193
Authors J. Taieb1, J.F. Emile2, K. Le Malicot3, E. Mini4, L. Petersen5, C. Lepage6, R. Salazar Soler7, P. Laurent-Puig8, H. Blons8
  • 1Assistance Publique Hôpitaux de Paris Department of Hepatogastroenterology and GI Oncology, Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris/FR
  • 2Hopital Ambroise Paré, Université de Versailles St Quentin en Yvelines, Boulogne Billancourt/FR
  • 3Fédération Francophone de Cancérologie Digestive, Dijon/FR
  • 4Department of Health Sciences, University of Florence, Florence/IT
  • 5Department of Oncology, Rigshopitalet, København/DK
  • 6Hepato-Gastroenterology Department Dijon University Hospital and INSERM U 866, Dijon/FR
  • 7Translational Research Laboratory and Department of Medical Oncology, Institut Catala d'Oncologia-IDIBELL, ĹHospitalet de Llobregat, Barcelona/ES
  • 8UMR-S1147, INSERM; Université Paris Descartes; Assistance Publique Hôpitaux de Paris Department of Biology, Paris/FR

Abstract

Introduction

The prognostic value of KRAS mutations in colon adenocarcinoma is controversial. We examined the prognostic impact of KRAS mutations in stage III patients receiving adjuvant FOLFOX +/- cetuximab from the PETACC8 Phase III trial.

Methods

KRAS exon2 mutations were examined in BRAF wild type tumors from patients enrolled in the PETACC8 trial. Because no effect from adjuvant cetuximab was reported, tumors from both study arms were pooled for analysis. Association between time to recurrence (TTR) and Disease-free survival (DFS) and KRAS mutation type was evaluated using Cox proportional hazard model.

Results

KRAS mutations were found in 638/1657 tumors. KRAS mutations in codon 12 (HR: 1.67; 95% confidence interval [CI] [1.35-2.04]; P < 0.001) but not in codon 13 (HR: 1.23; 95% confidence interval [CI] [0.85-1.79]; P = 0.26) were significantly associated with shorter TTR as compared to patients with KRAS/BRAF wild-type tumors, independently of other covariates. Taking anatomic sites into account, the impact of KRAS mutations on TTR was only found for distal tumors (n = 1043; 692 wild type; 351 mutated) with an increased risk of relapse (HR: 1.96; 95% confidence interval [CI] [1.51-2.56]; P < 0.0001) for KRAS codon 12 mutated tumors and a trend for codon 13 (HR: 1.59; 95% confidence interval [CI] [1.00-2.56]; P = 0.051). Similar results were found for DFS.

Conclusion

KRAS exon 2 mutations are independent predictors of TTR for patients with stage III distal CC receiving adjuvant therapy. Future clinical trials in the adjuvant setting should consider tumor location and KRAS mutations as important stratification factors.