Patients who received cetuximab (Erbitux) in combination with a standard adjuvant therapy for resected stage III colon cancer did not experience improved disease-free survival (DFS) or improved overall survival, according to the results of a trial that will be published in the Journal of the American Medical Association
In the multicenter Phase III trial, 2686 patients were randomized into two groups that received cetuximab and 12 biweekly cycles of leucovorin, fluorouracil, and oxaliplatin (FOLFOX) – specifically mFOLFOX6 – or mFOLFOX6 alone. Of those, 1863 had tumors exhibiting wild-type KRAS
mutations. Additionally, 717 patients with mutated KRAS
and 106 indeterminate KRAS
were enrolled in the study. Cetuximab is approved for patients with metastatic colon cancer, but only those who exhibit wild-type KRAS
The primary endpoint was DFS in patients with wild-type KRAS
mutations. After a median follow-up of 28 months (range, 0-68), the three-year DFS for wild-type KRAS
mutated patients who received mFOLFOX6 alone was 74.6% compared to 71.5% in those who received mFOLFOX6 and cetuximab (HR, 1.21; 95% CI, 0.98-1.49, P
= .08). In patients with mutated KRAS
, the DFS was 67.1% in the mFOLFOX6 alone group compared to 65.0% in the mFOLFOX6 plus cetuximab group (HR, 1.12; 95% CI, 0.86-1.46, P
= .38), there was no benefit observed in any subgroups.
For all ages that had wild-type KRAS
mutations or mutated KRAS
, overall survival at three years was 87.3% in the mFOLFOX6 only group compared to 85.6% in the mFOLFOX6 plus cetuximab group (HR, 1.25; 95% CI, 0.92-1.68, P
= .15). Adverse events of grade 3 or higher were more common in patients who received cetuximab than those who received only mFOLFOX6 (72.5% vs 52.3%; OR, 2.4, 95% CI, 2.1-2.8; P
< .001), and those receiving cetuximab were more likely to fail to complete 12 cycles of mFOLFOX6 (33% vs 23%; OR, 1.6; 95% CI, 1.4-1.9, P
“New approaches are needed to identify drugs that may be of benefit in adjuvant therapy, because as shown in our trial, promising activity in the metastatic setting did not translate into adjuvant therapy benefit and underscores the importance of performing clinical trials,” the authors wrote.
Cetuximab is a chimeric monoclonal antibody that specifically targets and inhibits epidermal growth factor receptor (EGFR). It is given as an intravenous infusion and has been approved to treat metastatic colon cancer that has been previously treated by chemotherapy as well as local or advanced squamous cell carcinoma of the head and neck when given in combination with radiation therapy. It is distributed by Bristol-Meyers Squibb and Eli Lilly and Company in North America.
Alberts SR, Sargent DJ, Nair S, et al. Effect of Oxaliplatin, Fluorouracil, and Leucovorin With or Without Cetuximab on Survival Among Patients With Resected Stage III Colon Cancer: A Randomized Trial. JAMA. 2012; 307(13):1383-1393.