467PD - Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin vs. capecitabine alone in locally advanced rectal c...

Date 10 October 2016
Event ESMO 2016 Congress
Session Gastrointestinal tumours, colorectal
Topics Surgical Oncology
Colon and Rectal Cancer
Therapy
Radiation Oncology
Presenter Hans Joachim Schmoll
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors H.J. Schmoll1, A. Stein2, R.D. Hofheinz3, T.J. Price4, B. Nordlinger5, J. Daisne6, J. Daisne6, J. Janssens7, B. Brenner8, P. Schmidt9, H. Reinel10, S. Hollerbach11, K. Caca12, F. Fauth13, J. Zalcberg14, S. Marreaud15, M. Mauer16, M. Lutz17, E. Van Cutsem18, K. Haustermans19
  • 1Dept. Hematology/ Oncology Fg 16 / U1, Martin Luther University of Halle, 06120 - Halle/DE
  • 2Medical Dpt, UKE Universitätsklinikum Hamburg-Eppendorf KMTZ, 20246 - Hamburg/DE
  • 3Interdisciplinary Tumorcenter, University Hospital Mannheim, 68167 Mannheim - Mannheim/DE
  • 4Haematology And Oncology, The Queen Elizabeth Hospital and University of Adelaide, 5011 - Adelaide/AU
  • 5Surgery, Hopital Ambroise Pare, 92104 Boulogne Bilancourt - Boulogne-Billancourt/FR
  • 6Radiotherapy, Clinique Ste Elisabeth, 5000 Namur - Namur/BE
  • 7Gastroenterology, AZ Turnhout - Campus Sint-Jozef, 2300 - Turnhout/BE
  • 8Institute Of Hematology, Rambam Health Care Center, Haifa/IL
  • 9Private Practice, OSP Onkologische Schwerpunktpraxis, 66538 - Neunkirchen/DE
  • 10Department Of Oncology, Leopoldina Krankenhaus Medizinische Klinik II, 97422 - Schweinfurt/DE
  • 11Gastroenterology, Allgemeines Krankenhaus Celle, 29223 Celle - Celle/DE
  • 12Department For Internal Medicine, Gastroenterology, Hemato-onkology, Klinikum Ludwigsburg Hämatologie/Onkologie, Palliativmedizin, 71640 - Ludwigsburg/DE
  • 13Private Practice, Onkologische Schwerpunktpraxis Hanau, 63450 - Hanau/DE
  • 14School Of Public Health & Preventive Medicine, Monash University, Melbourne/AU
  • 15Eortc Headquarters, European Organisation for research and treatment of Cancer (EORTC), 1200 - Brussels/BE
  • 16Gi Group, EORTC, 1200 - Brussels/BE
  • 17Dept. For Gastroenterology, Caritasklinik St. Theresia, 66113 Saarbrücken - Saarbruecken/DE
  • 18Digestive Oncology, University Hospitals Leuven - Campus Gasthuisberg, 3000 - Leuven/BE
  • 19Radiation Oncology, University Hospitals Leuven - Campus Gasthuisberg, 3000 - Leuven/BE

Abstract

Background

The PETACC-6 trial investigates whether the addition of oxaliplatin to preoperative oral fluoropyrimidine-based chemoradiation (CRT) followed by postoperative adjuvant fluoropyrimidine-based chemotherapy (CT) improves disease-free survival (DFS) in locally advanced rectal cancer.

Methods

Between 11/2008 and 09/2011, patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node-positive, with no evidence of metastatic disease and considered either resectable at the time of entry or expected to become resectable, were randomly assigned to receive 5 weeks of preoperative CRT with capecitabine, followed by 6 cycles of adjuvant CT with capecitabine with (arm 2) or without (arm 1) the addition of oxaliplatin before and after surgery. 440 DFS events were required to have 80% power to detect an improvement in 3-year DFS from 65% with capecitabine alone to 72% with capecitabine and oxaliplatin (HR = 0.763) using a two-sided alpha of 5% and owing for an interim analysis for early efficacy at 200 events. The primary analysis was intent-to-treat, adjusted for stratification factors (clinical T category, nodal status, distance from the tumor to the anal verge and method of locoregional staging) except center.

Results

1094 patients randomized (547 each arm); 543 eligible patients (arm 1), 526 (arm 2) started treatment; 67.4% completed protocol treatment in arm 1 vs. 53.8% in arm 2. Early analysis driven by the IDMC did not show a difference in 3 years in DFS and OS between both arms. The updated analysis 01/16 after a median follow-up of 52 months (86-55 months) again are not showing a difference with 76,5% in Arm 1 vs. 75,4% in arm 2 (HR 1,04, p = 0,744). Subgroup analysis showed superiority for DFS in nongerman participants (33%), whereas for german participants (67%) showed an inferior outcome (arm 1: HR 0,73, p= 0,061; arm 2: HR 1,35, p= 0,109), cape vs. cape/ox; 78,2% vs. 73,6% (arm1); 73,2% vs. 81,1% (arm 2). Multivariate analysis for identification of the confounding factors is ongoing and will be presented.

Conclusions

PETACC-6 does not show any benefit for the addition of oxaliplatin to capecitabine in contrast to the AIO / ARO / CAO trial and the Korean trial.

Clinical trial identification

NCT00766155 First received: October 2, 2008

Legal entity responsible for the study

EORTC

Funding

Roche

Disclosure

All authors have declared no conflicts of interest.