Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: Disease-free survival results at interim analysis.

3501 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 and adjusted for stratification factors (clinical T category, nodal status, distance from the tumor to the anal verge and method of locoregional staging) except the center. Results: 1094 patients were randomized (547 in each arm). 543 eligible patients in arm 1 and 526 in arm 2 started their allocated treatment of whom 67.4% completed protocol treatment in arm 1 vs. 53.8% in arm 2. An independent data monitoring committee reviewed the interim data and recommended the early release of the results. At median follow-up of 31 months, respectively 124 and 121 DFS events were observed in arm 1 and 2 (adjusted HR=1.036, 95% CI: 0.806 -1.331, P=0.781). 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%. Conclusions: Interim results indicate that the addition of oxaliplatin to capecitabine plus radiotherapy does not improve DFS. Careful follow-up should continue until the planned 440 events to document any late treatment difference. Clinical trial information: NCT00766155.