Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial

摘要: Summary Background Since the 1990s, fluorouracil-based adjuvant chemotherapy has significantly reduced risk of tumour recurrence in patients with stage III colon cancer. We aimed to assess whether addition cetuximab standard oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) cancer improved disease-free survival (DFS). Methods For this open-label, randomised phase 3 study done nine European countries, we enrolled through an interactive voice response system central randomisation centre, a stratified permuted block procedure. randomly assigned resected (R0) disease (1:1) receive 12 cycles FOLFOX4 twice week or without cetuximab. Patients were by N-status (N1 vs N2), T-status (T1-3 T4), obstruction perforation status (no no both). A protocol amendment (applied June, 2008, after 2096 had been treatment-restricted enrolment tumours wild-type at codons 13 exon 2 KRAS gene ( wild-type). The primary endpoint was DFS. Analysis intention treat all tumours. is registered EudraCT, number 2005-003463-23. Findings Between Dec 22, 2005, Nov 5, 2009, 2559 from 340 sites Europe assigned. Of these patients, 1602 (intention-to-treat population), 791 plus group 811 group. Median follow-up 3·3 years (IQR 3·2–3·4). In experimental control groups, DFS similar intention-to-treat population (hazard ratio [HR] 1·05; 95% CI 0·85–1·29; p=0·66), 2/ BRAF (n=984, HR 0·99; 0·76–1·28) 2-mutated (n=742, 1·06; 0·82–1·37). noted heterogeneous responses preplanned subgroup analyses. Grade 4 acne-like rash (in 209 785 [27%] four 805 [ 70 [9%]), mucositis (63 [8%] 10 [1%]), infusion-related reactions (55 [7%] 30 [4%]) more frequent treated than those who received alone. Interpretation did not improve compared alone This trial cannot conclude on benefit studied population, but heterogeneity suggests that further investigation role specific patient subgroups warranted. Funding Federation Francophone de Cancerologie Digestive (FFCD), Merck KGaA, Sanofi-Aventis.