572P - Prognostic value of KRAS mutations in stage III colon cancer: post-hoc analyses of the PETACC8 Phase III trial

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Translational Research
Presenter Hélène Blons
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors H. Blons1, J. Emile2, K. Le Malicot3, A. Zaanan4, J. Tabernero5, E. Mini6, G. Folprecht7, J. van Laethem8, J. Thaler9, J.A. Bridgewater10, L. Petersen11, E. Van Cutsem12, C. Lepage13, R. Salazar14, P. Laurent-Puig15, J. Taieb16
  • 1Biochemistry, Molecular Biology, HEGP Georges Pompidou Hospital, 75015 - paris/FR
  • 2Pathology, CHU Ambroise Pare, Paris/FR
  • 3Biostatistic, FFCD, 21079 - Dijon/FR
  • 4Gastroenterology, Hôpital Européen Georges Pompidou, APHP, Paris/FR
  • 5Medical Oncology Department, Vall d'Hebron University Hospital, ES-08035 - Barcelona/ES
  • 6Department Of Chemotherapy And Pharmacology, universita di Firenze, 50139 - Firenze/IT
  • 7Department Of Internal Medicine I, University Hospital Carl GustavTechnischen Univ.Dresden Medizinische, DE-01307 - Dresden/DE
  • 8Dept. Of Gastroenterology, Erasme(Free) University Hospital-(Universite Libre de Bruxelles), BE-1070 - Brussels/BE
  • 9Dept. Internal Medicine Iv, Klinikum der Kreuzschwestern Wels, 3956 - WELS/AT
  • 10Medical Oncology, UCL Cancer Institute, University College London, UK WC1E 6DD - LONDON/GB
  • 11Oncology, Rigshospitalet, 2100 - København/FR
  • 12Digestive Oncology, University Hospital Leuven, 3000 - Leuven/BE
  • 13Hepatogastroenterology Department, University Hospital, 21079 - DIJON Cedex/FR
  • 14G-i Unit. Medical Oncology Dpt., Institut Catal, ES-08907 - Barcelona/ES
  • 15Umr-s 1147 Personnalized Medecine, Pharmacogenomics And Therapeutic Optimization), Paris Descartes University, 75270 - Paris Cedex/FR
  • 16Gastroenterology And Digestive Oncology, Hopital Européen Georges Pompidou, 75015 - Paris/FR

Abstract

Aim

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 tumours from patients enrolled in the PETACC8 trial. Because no effect from adjuvant cetuximab was reported, tumours 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 tumours. 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 tumours, independently of other covariates. Taking anatomic sites into account, the impact of KRAS mutations on TTR was only found for distal tumours (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 tumours 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.

Conclusions

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 tumour location and KRAS mutations as important stratification factors.

Disclosure

J. Emile: received Honoraria from Merck-Serono; J. Tabernero: declared research funding from, and providing advisory roles for Amgen Merck KGaA and Sanofi; G. Folprecht: declared research funding from Merck KGaA and homoraria (advisory boards lectures) from Merck KGaA Roche Lilly and Amgen; J. Thaler: declared research funding and honororio for lectures from Sanofi and Merck; J.A. Bridgewater: declared advisory roles fro Merck, Sanofi and Roche; L. Petersen: declared advisory roles for Roche and Bayer; E. Van Cutsem: declared receiving research funding from Merck Serono paid to his institution; R. Salazar: declared providing advisory roles and lectures for sanofi Merck KGaA and Amgen; P. Laurent-Puig: declared providing advisory roles and lectures for Sanofi, Merck serono, amgen, Roche, Genomic Health, Myriad Genetics, and Pfizer; J. Taieb: declared research fundings from, and providing advisory roles and lectures for Sanofi, Merck KgaA. All other authors have declared no conflicts of interest.