Fluoropyrimidine-based chemotherapy plus the anti–vascular endothelial growth factor antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer.
Dr Jolien Tol and colleagues from the Netherlands studied the effect of adding the anti–epidermal growth factor receptor antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer.
|Median survival was 11 months with capecitabine, oxaliplatin, and bevacizumab|
|New England Journal of Medicine|
The research team randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab or the same regimen plus weekly cetuximab.
The primary end point was progression-free survival.
The mutation status of the KRAS gene was evaluated as a predictor of outcome.
The median progression-free survival was 11 months in the capecitabine, oxaliplatin, and bevacizumab group, and 9 in the same combined regimen plus weekly cetuximab group.
The researchers noted that quality-of-life scores were lower in the combined regimen plus weekly cetuximab group.
The overall survival and response rates did not differ significantly in the 2 groups.
The team noted that treated patients in the same regimen plus weekly cetuximab group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects.
Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had decreased progression-free survival as compared with cetuximab-treated patients with wild-type–KRAS tumors or patients with mutated-KRAS tumors in the capecitabine, oxaliplatin, and bevacizumab group.
Dr Tol’s team concludes, “The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life.”
“Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group.”