• Gastrointestinal Cancers
• Adjuvant/Neoadjuvant Therapy
• Oncology Clinical Trials

FOLFOX4 (leucovorin, 5-fluorouracil, and oxaliplatin) has been the standard adjuvant therapy for resected stage III colon cancer since 2004, producing 3-year disease-free survival (DFS) rates of ∼70%. The aim of the Combination Chemotherapy with or Without Cetuximab in Treating Patients with Stage III Colon Cancer That Was Completely Removed by Surgery [PETACC-8; NCT00265811] trial presented by Julien Taïeb, MD, PhD, Hôpital Européen Georges Pompidou, Paris, France, was to assess the potential benefit of adding cetuximab to standard treatment for colon cancer.

Patients with fully resected stage III colon cancer were randomized to FOLFOX4 every 2 weeks, with or without cetuximab (initial dose, 400 mg/m²; 250 mg/m² weekly; Days 1 and 8), for 12 cycles. The primary endpoint was DFS in patients with KRAS wild-type (WT) tumors. The secondary endpoints were overall survival (OS), and treatment compliance and toxicity. A preplanned subgroup analysis focused on demographic, oncologic, and molecular data. An interim analysis was planned after 65% of planned events occurred.

At interim analysis, 2559 patients were enrolled, 62.5% of whom had KRAS WT tumors. A total of 1602 patients of these patients were randomized. The median follow-up for DFS was 3.33 years in the FOLFOX4 plus cetuximab arm and 3.30 years in the FOLFOX4 alone arm. Baseline characteristics were similar in both arms.

The 3-year DFS rate was 75.1% with FOLFOX4 plus cetuximab versus 78.0% with FOLFOX4 alone (HR, 1.047; 95% CI, 0.853 to 1.286; p=0.6562). The OS rate was 88.3% with FOLFOX4 plus cetuximab versus 90.5% with FOLFOX4 alone (HR, 1.092; 95% CI, 0.813 to 1.466; p=0.5583). Grade 3/4 adverse events occurred in 80.9% of patients treated with FOLFOX4 plus cetuximab versus 66.2% of those treated with FOLFOX4 alone. Patients with KRAS/BRAF WT tumors treated with FOLFOX4 plus cetuximab (n=492) versus FOLFOX4 alone (n=492) had no significant differences in DFS (115 vs 108 events; HR, 0.985; 95% CI, 0.755 to 1.284; p=0.9117) or OS (55 vs 52 events; HR, 0.981; 95% CI, 0.669 to 1.438; p=0.9236).

Worse DFS outcomes in patients treated with FOLFOX4 plus cetuximab versus FOLFOX4 alone were observed in females (adjusted HR, 1.45; 95% CI, 1.03 to 2.03; p=0.031), patients aged >70 years (adjusted HR, 1.97; 95% CI, 0.99 to 3.93; p=0.051), and patients with right-sided tumors (adjusted HR, 1.40; 95% CI, 1.01 to 1.94; p=0.043). Patients with pT4N2 tumors treated with FOLFOX4 plus cetuximab (n=79) versus FOLFOX4 alone (n=67) had significantly better DFS (32 vs 41 events; HR, 0.555; 95% CI, 0.348 to 0.885; p=0.0122).

Adding cetuximab to FOLFOX4 offered no DFS or OS benefit to patients with resected stage III KRAS WT or KRAS/BRAF WT colon cancer. Subgroup analyses suggested that patients with pT4N2 tumors may benefit from treatment with cetuximab, while females, patients aged >70 years, and patients with right-sided colon cancer may have worse outcomes with cetuximab—results that, according to Prof. Taïeb, suggest stage III and IV colon cancers have a different biology. Microsatellite instability status is being determined to explore interaction with poor outcomes in the 3 latter subgroups.

• © 2012 MD Conference Express®