• Gastrointestinal Cancers
• Reproductive Cancers Clinical Trials

• Gastrointestinal Cancers
• Reproductive Cancers Clinical Trials

Treatment options for locally advanced rectal cancer include chemotherapy, surgery, and radiation therapy. It is not known if adding oxaliplatin to capecitabine would increase the efficacy of chemotherapy for patients with locally advanced rectal cancer. Hans-Joachim Schmoll, MD, PhD, Martin Luther University Halle-Wittenberg, Halle, Germany, reported the disease-free survival (DFS) results from the interim analysis of Chemotherapy and Radiation Therapy Before Surgery Followed by Capecitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced Rectal Cancer [PETACC-6; NCT00766155].

PETACC-6 is a randomized, Phase 3 trial to determine if the addition of oxaliplatin to preoperative oral fluoropyrimidine-based chemoradiation (CRT) followed by postoperative adjuvant fluoropyrimidine-based chemotherapy (CT) improves DFS in patients with locally advanced rectal adenocarcinoma [Schmoll HJ et al. Ann Oncol 2014 (abstr O-0017)]. PETACC-6 enrolled 1094 patients with rectal adenocarcinoma within 12 cm from the anal verge that was T3 or T4 and/or node-positive, nonmetastatic, and either resectable at the time of enrollment or expected to become resectable. Patients were randomly assigned 1:1 to receive 5 weeks of preoperative CRT with capecitabine, followed by 6 cycles of adjuvant CT with capecitabine (arm 1) or capecitabine plus oxaliplatin (arm 2) before and after surgery.

DFS was defined as the time from random assignment to the first event of loco-regional failure, distant failure, the appearance of a secondary cancer, or death. Unresectable tumors or distant metastases that were discovered at surgery were deemed failures at the time of surgery. To detect an increase in 3-year DFS with 80% power from 65% with capecitabine alone to 72% with capecitabine plus oxaliplatin (HR, .763) using a 2-sided alpha of 5%, 440 events were required; an interim analysis for early efficacy required 200 events.

Of the 547 patients in each arm, 543 in arm 1 and 528 in arm 2 began preoperative treatment (3 patients in arm 2 did not receive oxaliplatin); of these patients, 420 (77.3%) in arm 1 and 381 (72.6%) in arm 2 began postoperative chemotherapy per protocol. In arm 2, 45 patients (11.8%) did not receive postoperative oxaliplatin. Reasons for treatment discontinuation included progressive disease (3.9% in arm 1 vs 3.8% in arm 2), toxicity (7.7% vs 16.5%), complications of surgery (8.7% vs 9.1%), and patient refusal (5.9% vs 10.8%).

At the planned interim analysis, with a median follow-up of 31 months, there were 124 DFS events in arm 1 and 121 DFS events in arm 2 (adjusted HR, 1.036; 95% CI, 0.806 to 1.331; p = .781). The 3-year DFS in arm 1 was 74.5% (95% CI, 70.1% to 78.3%), which was higher than anticipated. The 3-year DFS in arm 2 was 73.9% (95% CI, 69.5% to 77.8%). The conditional power for the HR of 0.763 was only 7%. With 245 DFS events at 31 months of follow-up, another 2 years of follow-up is estimated for accumulation of the required 440 events.

At the interim analysis, adding oxaliplatin to preoperative capecitabine-based CRT and postoperative adjuvant CT did not result in a DFS benefit for patients with locally advanced rectal adenocarcinoma.

• © 2014 MD Conference Express®