ACCORD12/0405-Prodige 2 phase III trial neoadjuvant treatment in rectal cancer: Results after 5 years of follow-up.

Abstract

490 Background: The ACCORD 12 randomized trial was aiming at improving ypCR by increasing the radiation dose and adding oxaliplatin (OX) to a standard RT 45 Gy with concurrent capecitabine. On short term benefit of OX was not demonstrated (Gérard JP et al. J Clin Oncol. 2010;28:1638-44) at 3 years no significant difference in clinical outcome was achieved (Gérard JP et al. J Clin Oncol. 2012;30:4558-65. François E et al. Radiother Oncol. 2014;110:144-9). This is an update of results at 5 years. Methods: Between 11/2005 and 07/2008, 598 patients were randomized. Inclusion criteria: adenocarcinoma of rectum accessible to digital examination, T3 Nx M0 (or T2 distal anterior rectum). Randomization was between two neoadjuvant treatments chemo radiotherapy: Cap45 (45 Gy + capecitabine) and Capox50 (50 Gy + cape. and oxaliplatin). Main end point was sterilization of the operative specimen. Bowel function for patients treated with anterior resection was analyzed with a global score (1 very poor to 7 excellent). A total of 253 patients received adjuvant chemotherapy usually with FOLFOX: 133 in Cap45, 120 in Capox50. Results: In the ITT population, with a median follow-up of 60 months, updated carcinologic results were calculated using the Kaplan-Meier method. Out of 299 pts randomized in CAP45 and 299 pts in CAPOX50 results were respectively the following 1) 5y-cumulative incidence of Loc. Recurrence : 8.8% vs 7.8% (p = 0.78 HR = 0.92 [0.51-1.66]) 2) 5y-cumulative incidence of dist metastasis : 29.3% vs 27.1% (p = 0.48 HR = 0.89 [0.62-1.54]) 3) 5y-disease free survival rate : 60.4% vs 64.7% (p = 0.25 HR = 0.86 [0.66-1.11]) 4) 5y-overall survival rate : 76.4% vs 81.9% (p = 0.06 HR = 0.71 [0.50-1.01]) 5) bowel function median score : 5.2 [1-7] vs 4.9 [1-7]. Conclusions: At 5 years there was no significant difference in terms of local recurrence or distant metastases rates between both regimens. The new finding is a trend for improved overall survival in the Capox 50 groups may be related to subsequent salvage secondary treatments. At time of meeting the prognostic factors will be available in details and these results put in perspective with other phase III trial testing the role of oxaliplatin in Europe and the US. Clinical trial information: NCT00227747.