505PD - Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine +/- oxaliplatin in locally advanced rectal cancer: Interim analysis...

Date 27 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, colorectal
Topics Anticancer Agents
Surgical Oncology
Colon and Rectal Cancer
Biological Therapy
Radiation Oncology
Presenter Hans Joachim Schmoll
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors H.J. Schmoll1, K. Haustermans2, T.J. Price3, B. Nordlinger4, R. Hofheinz5, J. Daisne6, J.F. Janssens7, B. Brenner8, P. Schmidt9, H.H. Reinel10, S. Hollerbach11, K. Caca12, F.W.B. Fauth13, C.V. Hannig14, J. Zalcberg15, N. Tebbutt16, M. Mauer17, C.G.M. Messina18, M.P. Lutz19, E. Van Cutsem20
  • 1Dept. Hematology/ Oncology, University of HalleMartin Luther University Hospital, DE-06120 - Halle/DE
  • 2Radiation Oncology, University Hospitals Leuven - Campus Gasthuisberg, 3000 - Leuven/BE
  • 3Medical Oncology, The Queen Elizabeth Hospital and University of Adelaide, 5012 - Woodville South/AU
  • 4Department Of Surgery, Hôpital Ambroise Paré, 92100 - Boulogne Billancourt/FR
  • 5Medical Oncology, Universitätsmedizin Mannheim, Universität Heidelberg, 68167 - Mannheim/DE
  • 6Radiation Oncology, Clinique & Maternité Ste-Elisabeth, BE-5000 - Namur/BE
  • 7Gastroenterology, St Elisabethziekenhuis-Turnhout, BE-2300 - Turnhout/BE
  • 8Institute Of Oncology, RABIN MEDICAL CENTER - TEL AVIV UNIVERSITY, Petah Tiqva/IL
  • 9Haematologie / Onkologie, OSP Onkologische Schwerpunktpraxis, DE-66538 - Neunkirchen/DE
  • 10Medizinische Klinik Ii - Internistische Onkologie, Leopoldina KrankenhausMedizinische Klinik II, DE-97422 - Schweinfurt/DE
  • 11Dept Of Gastroenterology, ALLGEMEINES KRANKENHAUS CELLE, Celle/DE
  • 12Medizinische Klinik I, KLINIKUM LUDWIGSBURG, Ludwigsburg/DE
  • 13Haematologie / Onkologie, ONKOLOGISCHE SCHWERPUNKTPRAXIS, DE- - Hanau/DE
  • 14Innere Medizin, Hämatologie Und Internistische Onkologie, Schwerpunktpraxis für Hämatologie und Onkologie, Bottrop/DE
  • 15Haematology And Medical Oncology, Peter MacCallum Cancer Center, AU-3002 - Melbourne/AU
  • 16Medical Oncology, Austin Health, Melbourne/AU
  • 17Department Of Statistics, EORTC, Brussels/BE
  • 18Medical Department, European Organisation for Research and Treatment of Cancer (EORTC AISBL), 1200 - Brussels/BE
  • 19Medizinische Klinik, Caritasklinik St. Theresia, 66113 - Saarbrücken/DE
  • 20Internal Medicine, University Hospitals Leuven - Campus Gasthuisberg, 3000 - Leuven/BE



The PETACC-6 trial investigates the role of oxaliplatin in addition to preoperative chemoradiation (CRT) and adjuvant chemotherapy (CT) with capecitabine to improve disease-free survival (DFS) in locally advanced rectal cancer.


Patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node-positive, without evidence of metastatic disease, considered either resectable at the time of entry or expected to become resectable, were randomized to 5 weeks of preoperative CRT with capecitabine, followed by surgery and 6 cycles of adjuvant CT with capecitabine (standard control arm 1) or capecitabine + oxaliplatin before and after surgery (arm 2). 440 DFS events were required to have 80% power to detect an improvement in 3-year DFS from 65% to 72% (HR = 0.763), with two-sided alpha of 5% and allowing for an interim analysis for early efficacy at 200 events.


1094 patients were randomized (547 in each arm). From 1081 eligible patients, 543 in arm 1 and 528 in arm 2 started preoperative treatment (3/528 patients without oxaliplatin in arm 2), and of these 77.3% and 72.6%) patients started postoperative chemotherapy within protocol. In arm 2, 11.8% patients did not receive the planned postoperative oxaliplatin. Major reasons for protocol discontinuation were progressive disease (3.9% in arm 1 vs. 3.8% in arm 2), toxicity (7.7% vs. 16.5%), surgery complication (8.7% vs. 9.1%), patient's refusal (5.9% vs. 10.8%). At planned interim analysis, the independent data monitoring committee recommended the early release of the results. At a median follow-up of 31months, 124 and 121 DFS events were observed in arm 1 and 2 (adjusted HR = 1.036, 95% CI: 0.81 -1.33, P = 0.78). 3-year DFS was 74.5% (95% CI: 70.1% - 78.3%) in arm 1 (which is higher than anticipated) vs. 73.9% (95% CI: 69.5% - 77.8%) in arm 2; conditional power under HR = 0.763 is only 7%. Less locoregional and distant failures were recorded in the experimental arm with oxaliplatin (95 in arm 2 vs. 109 in arm 1) but a higher rate of deaths without progression (26 in arm 2 vs. 15 in arm 1).


Interim results at a median follow up of 2.6 y currently indicate no DFS-benefit for the addition of oxaliplatin to capecitabine-based CRT and adjuvant CT. However, with actually only 245 out of the required 440 events, final evaluation cannot be done before at least 2 further years follow-up.


H.J. Schmoll: has a consultant or advisory relationship to disclose with Roche, Sanofi and Bayer; has honoraria to disclose from Roche; has research funding to disclose from Merck and Roche; K. Haustermans: has research funding to disclose from Roche; T.J. Price: has a consultant or advisory relationship to disclose with Roche; R. Hofheinz: has a consultant or advisory relationship to disclose with Roche; has honoraria and research funding to disclose from Roche; B. Brenner: has a consultant or advisory relationship to disclose with Sanofi-Aventis; has research funding to disclose from Sanofi-Aventis; J. Zalcberg: has a consultant or advisory relationship to disclose with Sanofi-Aventis and Roche; has honoraria, research funding and other remuneration to disclose from Sanofi-Aventis and Roche. M.P. Lutz: has a consultant or advisory relationship to disclose with Roche; E. Van Cutsem: has research funding to disclose from Roche and Sanofi.All other authors have declared no conflicts of interest.