Cetuximab Increases Survival in Advanced Colorectal Cancer Patients, Studies Show

PHILADELPHIA -- Research presented today at the 2007 Annual Meeting of the American Association for Cancer Research confirmed that there is now an effective treatment option for colorectal cancer patients for whom all other treatment options have been exhausted - cetuximab.

In a study of 572 colorectal cancer patients, researchers in Canada, Australia, New Zealand and Singapore found that cetuximab, marketed under the brand-name Erbitux®, improved survival time and slowed progression of the disease. Support for the study was provided by Bristol-Myers Squibb Company and ImClone Systems Incorporated.

“Cetuximab improved survival in these patients when all other therapies had failed,” said Derek Jonker, M.D., assistant professor at the University of Ottawa and Canadian co-chair of the study. “This is the first time a single agent biologically targeted therapy has demonstrated a survival advantage in patients with colorectal cancer, and it is also the first time an EGFR-targeting drug has achieved this goal.”

Conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) in collaboration with the Australasian Gastro-Intestinal Trials Group (AGITG), the study, called CO.17, was a randomized, multi-center, phase III trial. It compared cetuximab plus best supportive care to best supportive care alone in patients with metastatic colorectal cancer whose disease was no longer responding to all available chemotherapy, including irinotecan, oxaliplatin and fluoropyrimidines.

The goal of the CO.17 study was to evaluate the effect of cetuximab on survival in patients with advanced colorectal cancer who are without other options for treatment other than supportive care.

Study participants were randomly selected either to receive best supportive care alone, or best supportive care plus cetuximab intravenously weekly until the cancer progressed further. According to Jonker, the researchers defined best supportive care as any and all care given to alleviate symptoms of the cancer and to improve quality of life. The participants who were to receive cetuximab were given 400 mg of the drug intravenously at the outset of the trial, followed by weekly doses of 250 mg.

Cetuximab, an antibody against the epidermal growth factor receptor (EGFR), functions by binding to the receptor on the surface of cancer cells. This binding action prevents the activation of enzymatic pathways that lead to cell growth and proliferation. Cetuximab also enlists the body’s immune system triggering “natural killer cells” to attack the cancer, a process called antibody dependent cell cytotoxicity.

Jonker and his colleagues followed the patients, assessing the status of the tumors every eight weeks by CT scan until the cancer began to progress. According to Jonker, the results of the CO.17 trial showed a statistically significant 23 percent improvement in overall survival (the primary outcome being studied) as well as a 32 percent reduction in the risk of disease progression (the secondary outcome being studied). The survival time of the participants was, on average, six months for the patients given cetuximab versus four-and-a-half months for patients who received best supportive care alone.

“Earlier studies demonstrated cetuximab could shrink colon tumors, both alone and when combined with chemotherapy,” Jonker said. “While some patients receiving cetuximab in the CO.17 study had significant tumor shrinkage, many more had the cancer growth arrested, delaying progress of the disease and resulting in patients living longer.”

“These promising results,” Jonker said, “will lead to further National Cancer Institute of Canada trials in which cetuximab will be combined with other therapeutics to treat metastatic colorectal cancer.”