As reported in the Journal of Clinical Oncology by Schmoll et al, the phase III PETACC 6 trial has shown no benefit of the addition of preoperative and adjuvant oxaliplatin to preoperative capecitabine-based chemoradiation and adjuvant capecitabine in patients undergoing total mesorectal excision for locally advanced rectal cancer.
The open-label trial included 1,068 eligible patients from sites in Australia, Belgium, France, Germany, Israel, and New Zealand. They were randomly assigned between November 2008 and September 2011 to receive 5 weeks of preoperative capecitabine-based chemoradiation (45–50.4 Gy) followed by six cycles of adjuvant capecitabine without (control group, n = 543) or with preoperative oxaliplatin and six cycles of adjuvant oxaliplatin (CAPOX group, n = 525).
Patients had rectal adenocarcinoma within 12 cm from the anal verge and T3/4 or node-positive disease. The primary endpoint was improvement of 3-year disease-free survival by oxaliplatin from 65% to 72% (hazard ratio [HR] = 0.763).
Protocol treatment was completed by 68% of patients in the control group vs 54% in the CAPOX group. At a median follow-up of 68 months, disease-free survival events were observed in 157 patients in the control group and 156 in the CAPOX group (adjusted HR = 1.02, 95% confidence interval = 0.82–1.28, P = .835).
Disease-free survival at 3 years was higher than expected in the control group (76.5%, higher than the anticipated 65%) vs 75.8% in the CAPOX group. Disease-free survival at 7 years was 66.1% vs 65.5% (HR =1.02, P = .861). No difference in overall survival was observed at 5 years (83.1% vs 80.1%) or 7 years (73.5% vs 73.7%, HR = 1.19, P = .205).
Subgroup analyses indicated heterogeneity in treatment effect according to treatment in German vs non-German sites. At German sites (n = 737), the CAPOX group had decreased disease-free survival at 5 years (73.4% vs 67.8%, HR = 1.27, P = .092); at non-German sites, the CAPOX group had an increased rate (67.0% vs 75.7%, HR = 0.70, P = .061). This difference remained significant on multivariate analysis.
Grade 3 or 4 adverse events occurred in 14.4% of patients in the control group and 37.3% of patients in the CAPOX group during neoadjuvant treatment, and in 23.4% vs 46.6% during adjuvant treatment. Grade 3 or 4 gastrointestinal adverse events occurred in 7.9% vs 21.7% during neoadjuvant treatment and in 7.6% vs 22.6% during adjuvant treatment. Grade 2 to 4 neuropathy occurred in 0.2% vs 9.1% and in 2.9% vs 33.7%, respectively.
The investigators concluded, “The addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative adjuvant chemotherapy impairs tolerability and feasibility and does not improve efficacy.”
Hans-Joachim Schmoll, MD, PhD, of Martin Luther University, Halle, Germany, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the European Organisation for Research and Treatment of Cancer, Australasian Gastro-Intestinal Trials Group, Hoffmann-La Roche, Pfizer, and others. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.