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04-04-2012 | Surgery | Article

No benefit of adding cetuximab to chemotherapy in resected colon cancer

Abstract

Free abstract

MedWire News: The addition of cetuximab to chemotherapy fails to improve disease-free survival in patients who undergo surgery for colon cancer, US researchers say.

For Steven Alberts (Mayo Clinic, Rochester, Minnesota) and colleagues, the promising activity of cetuximab in the metastatic setting failed to translate into an adjuvant therapy benefit.

Cetuximab, an anti-epidermal growth factor receptor monoclonal antibody, has been shown to provide clinical benefit when added to chemotherapy, as well as when used as a single agent, in patients with metastatic colorectal cancer.

Given the success of the agent in patients with metastatic cancer, the researchers tested the potential benefit of adding cetuximab to the modified sixth version of the FOLFOX (leucovorin, fluorouracil, and oxaliplatin) regimen in 2686 patients with resected stage III wild-type KRAS colon cancer.

Publishing their findings in the Journal of the American Medical Association, the authors report there was no significant treatment benefit of adding cetuximab to the modified FOLFOX regimen (mFOLFOX6).

Among patients with wild-type KRAS colon cancer, the three-year rate of disease-free survival was 74.6% in patients treated with mFOLFOX6 alone and 71.5% among those treated with cetuximab and mFOLFOX6.

Overall, grade 3 or higher adverse events occurred in half of patients receiving mFOLFOX6 alone and in 73.3% of those receiving cetuximab and chemotherapy (odds ratio 2.6). Grade 3 or higher toxicities occurred in 72% of patients younger than 70 years old and in 81% of those aged 70 years of age and older.

In fact, patients 70 years of age and older who received cetuximab actually had worse clinical outcomes than placebo-treated patients.

Previous analyses have shown that colon cancers with mutations in the KRAS gene are refractory to cetuximab and that only patients with tumors with the wild-type gene have the potential to respond. Of those with mutated KRAS, the three-year rate of disease-free survival was 65.0% in the cetuximab arm and 67.1% in those treated with mFOLFOX6 only.

Although the role of adjuvant therapy is to eliminate micrometastatic disease, "the ability of cetuximab to enhance the benefit of chemotherapy appears to be complex," according to Alberts and colleagues.

In an editorial, Neil Segal and Leonard Saltz (Memorial Sloan-Kettering Cancer Center, New York, USA) said the negative findings disappointed many given the success of cetuximab observed in the metastatic setting.

The clinical implications, according to the editorialists, are clear: the way in which chemotherapy kills tumor cells in macrometastases differs from how adjuvant therapy accomplishes this in micrometastases.

"The inescapable conclusion is that efficacy in the metastatic setting does not reliably predict efficacy in the adjuvant setting," they write.

By MedWire Reporters

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