LBA4 - Adjuvant FOLFOX4 with or without cetuximab (CTX) in patients (pts) with resected stage III colon cancer (CC): DFS and OS results and subgroup analys...

Date 30 September 2012
Event ESMO Congress 2012
Session Presidential Symposium I
Topics Anticancer agents
Colon and Rectal Cancer
Biological Therapy
Presenter Julien Taieb
Authors J. Taieb1, J. Tabernero2, E. Mini3, F. Subtil4, G. Folprecht5, J. van Laethem6, J. Thaler7, J.A. Bridgewater8, E. Van Cutsem9, P. Rougier10, L. Collette11, M. Praet12, M. Schneider4, O. Bouché13, C. Lepage14, C. Girault15, J. Emile16, P. Laurent-Puig17, L. Bedenne18
  • 1Gastroenterology And Digestive Oncology, Hopital Européen Georges Pompidou, 75015 - Paris/FR
  • 2Oncology Department, Vall d'Hebron University HospitalMedical Oncology Service, ES-08035 - Barcelona/ES
  • 3Department Of Chemotherapy And Pharmacology, universita di Firenze, 50139 - Firenze/IT
  • 4Data Center, FFCD, 21079 - DIJON Cedex/FR
  • 5Department Of Internal Medicine I, University Hospital Carl GustavTechnischen Univ.Dresden Medizinische, DE-01307 - Dresden/DE
  • 6Dept. Of Gastroenterology, Erasme(Free) University Hospital-(Universite Libre de Bruxelles), BE-1070 - Brussels/BE
  • 7Dept. Internal Medicine Iv, Klinikum der Kreuzschwestern Wels, 3956 - WELS/AT
  • 8Paul O'gorman Building, UCL Cancer Institute, UK WC1E 6DD - LONDON/UK
  • 9Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven/BE
  • 10Service D'hépato-gastro-entérologie, Hôpital Européen Georges Pompidou, 75015 - Paris/FR
  • 11Statistics Department, EORTC, Brussels/BE
  • 12-, EORTC, Brussels/BE
  • 13Service d'Hépato-gastroentérologie et de Cancérologie Digestive, Rheims/FR
  • 14Service D'hge, CHU Le Bocage, 21079 - Dijon Cedex/FR
  • 15-, FFCD, Dijon Cedex/FR
  • 16Service De Pathologie, Hôpital Universitaire Ambroise Paré, APHP & Université Versailles SQY, 92104 - Boulogne/FR
  • 17Bases Moléculaires De Réponse Aux Xénobiotiques, Unité 775, Faculté de Médecine des Saints Pères, Paris/FR
  • 18Hepatogastroenterology Department, University Hospital, 21079 - DIJON Cedex/FR



Background: The potential benefit of adding CTX to the current standard treatment for stage III CC, was assessed. Subgroup analyses of demographic, oncologic and molecular data may improve our understanding of this patient population. Methods: CC pts were randomized 28-56 days following resection. They received 12 biweekly cycles of oxaliplatin 85 mg/m2 day (d) 1, with leucovorin 200 mg/m2, 5-FU 400 mg/m2 bolus IV, followed by 5-FU 600 mg/m2 22-hr IV on d1-2 (FOLFOX4), without (arm A) or with weekly CTX (arm B) 250 mg/m2 (initial dose 400 mg/m2, cycle 1). Primary endpoint was disease free survival time (DFS). Secondary endpoints included overall survival (OS), treatment compliance and safety. Planned accrual of 1,407 KRAS wild-type (wt) pts provided 90% power to detect a hazard ratio (HR) of 0.75 with 2-sided a=0.05, with interim analyses after 65% of planned events. Preplanned subgroup analyses were performed. Results: 1,602 KRAS wt pts (811 arm A, 791 arm B), were randomized. BRAF status was determined in 1134 (71%) KRAS wt pts; median follow-up ~40 months. This interim analysis showed no difference between arms for DFS (HR 1.047, 95% CI 0.85, 1.29; p=0.66) or OS (HR 1.09, 95% CI 0.81, 1.46; p=0.55) in KRAS wt pts or for DFS (HR 0.985, 95% CI 0.75, 1.28; p=0.91) or OS (HR 0.98, 95% CI 0.67, 1.44; p=0.92) in KRAS/BRAF wt pts (n=984). Worse outcomes were seen with CTX in pts >70 years (n=149, DFS: HR 1.97, 95% CI 0.99, 3.93; p=0.051), in females (n=666, HR 1.45, 95% CI 1.03, 2.02; p=0.03) and pts with right-sided CC (n=570, HR 1.40, 95% CI 1.01, 1.94; p=0.04). Conversely, a trend towards a better outcome was seen in pts with poor prognosis tumors (high grade, T4, N2, perforation/obstruction, VELI+) and was significant in pts with pT4N2 at diagnosis (n=146, HR 0.55, 95% CI 0.35-0.88; p=0.01). Conclusions: In this trial adding CTX to FOLFOX4 offered no benefit to pts with resected stage III KRAS wt and KRAS/BRAF wt CC. Subgroup analyses in this large population suggest that pts with pT4N2 tumors may receive some benefit from CTX in this setting. MSI status determination is ongoing to explore its interaction with poor outcome in female pts and those with right-sided tumors. Supported by Merck-Serono, Sanofi-Aventis. ?