(ChemotherapyAdvisor) – Adding cetuximab to adjuvant FOLFOX4 did not show a benefit in patients with resected stage III KRAS mutant (mKRAS) colorectal cancer, results of a randomized phase 3 trial reported during the European Society for Medical Oncology 2012 Congress in Vienna, Austria.
The rationale for the European Pan-European Trials in Alimentary Tract Cancer (PETACC) 8 Intergroup Trial was based on a previous finding that adding cetuximab to FOLFOX was beneficial in patients with metastatic KRAS wild-type (wt) colon cancer. However, these negative results echo those of the US N0147 study, which also failed to show a benefit when cetuximab was added to mFOLFOX6, reported Dr. Julien Taieb of the Georges Pompidou European Hospital, Paris, France.
Patients were randomized 28-56 days following resection to 12 biweekly cycles of oxaliplatin 85mg/m2 on day 1, with leucovorin 200mg/m2 and 5-FU400 mg/m2 bolus IV followed by 5-FU 600mg/m2 over 22 hours IV on days 1-2 (FOLFOX4), without (arm A) or with (arm B) weekly cetuximab 250 g/m2 (loading dose 400mg/m2).
At a median follow-up of 45.4 months, no difference was observed between the arms for disease-free survival (DFS; HR 1.06; 95% CI, 0.82–1.37; P=0.65). Three-year DFS was 71.0% (95% CI, 66.0–75.3) in arm A and 70.7% (95% CI 65.6–75.1) in arm B.
Grade 3 or higher adverse events were significantly increased in arm B (81%) vs arm A (68.4%; RR 1.18; 95% CI, 1.09–1.29), as were diarrhea, asthenia, mucositis, skin disorders (grade ≥3) and failure to complete 12 cycles.
Dr. Taieb noted that “cetuximab may have a different form of activity in micrometastatic disease compared with that observed in stage IV disease” as a possible explanation for why cetuximab did not provide any additional benefit in this setting.
The study was supported by Merck-Serono and Sanofi-Aventis.