For patients with KRAS wild-type untreated colorectal cancer, adding cetuximab or bevacizumab to combination chemotherapy offers equivalent survival, researchers said at the European Society for Medical Oncology 16th World Congress on Gastrointestinal Cancer in Barcelona, Spain.

“The CALGB/SWOG 80405 trial was designed and formulated in 2005, and the rationale was simple: we had new drugs, bevacizumab and cetuximab, and the study was designed to determine if one was better than the other [as a first-line treatment] for patients with colon cancer,” said lead study author Alan P. Venook, MD, distinguished Professor of Medical Oncology and Translational Research at the University of California, San Francisco.

The CALGB/SWOG 80405 trial studied patients whose tumors were KRAS wild-type at codons 12 and 13. Patients received mFOLFOX6 or FOLFIRI at the discretion of their doctor and were randomized to cetuximab (578 patients) or bevacizumab (559 patients).

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“There was no meaningful difference in outcome between treatment arms,” said Venook. “In both arms patients lived close to 30 months. About 10% of patients lived more than 5 years. Overall patients did much better than anticipated and it was indifferent to the type of treatment.”

Because almost 75% of the patients received mFOLFOX6 as the chemotherapy, the interaction between the experimental drugs and chemotherapy will be limited, but an analysis is underway. The investigators are also conducting molecular analyses that may identify subsets of patients who did better or worse on either treatment.

“This was a long awaited phase III trial with a head-to-head comparison of two different molecular approaches: epidermal growth factor receptor (EGFR) blocking by cetuximab on one side and antiangiogenic (antivascular endothelial growth factor [VEGF]) inhibiting treatment with bevacizumab on the other side, both in combination with any standard first-line chemotherapy in metastatic colorectal cancer. The trial is important because the primary endpoint was overall survival. The FIRE-3 trial presented last year indicated that there may be an overall survival benefit with cetuximab but overall survival was only a secondary end point and data was inconclusive,” said ESMO spokesperson Dirk Arnold, MD, Director of the Department of Medical Oncology, Tumour Biology Centre in Freiburg, Germany.

“Each of the monoclonal antibodies, in combination with standard chemotherapy, gave an overall survival of about 30 months: this is the longest overall survival in such a large trial and clearly sets the standard,” Arnold continued. “We now know that using any monoclonal antibody with any standard chemotherapy in first-line treatment may give the patient the likelihood of surviving about 30 months. However there is no clear winner in terms of