Colon Cancer Drug Won't Help Those With Certain Gene Mutation

A new study suggests that people with advanced colon cancer who have a particular gene mutation won't benefit from the medication cetuximab (Erbitux).

While the drug can add months to the lives of people without a mutation in a gene called K-ras, those who have the mutation won't see any benefit from this additional therapy, reports the study, which is published in the Oct. 23 issue of the New England Journal of Medicine.

"We believe that, in the context of pre-treated advanced bowel cancer, the K-ras mutation status of the cancer should be determined before using cetuximab, and cetuximab should only be given to patients with tumors that do not have the mutation," said study author Dr. Christos S. Karapetis, a senior consultant medical oncologist and director of clinical research in the department of medical oncology at Flinders Medical Centre in Australia.

Karapetis said that about four in 10 people with colon cancer have the K-ras mutation.

Erbitux works by interrupting cell growth and division. It does this by binding to a receptor known as epidermal growth factor receptor (EGFR). A mutation in the K-ras gene is believed to interfere with cetuximab's ability to disrupt EGFR, according to the study.

For the study, 572 people with advanced colorectal cancer were randomly assigned to receive either weekly treatment with cetuximab and supportive care (287 people) or supportive care alone (285 people). All had undergone other treatment options without success.

Almost 400 tumor specimens from the study volunteers were tested for K-ras mutations (198 from the cetuximab group and 196 from the supportive care group). Just over 42 percent of the tumors evaluated were found to have mutations in the K-ras gene.

Even with cetuximab treatment, people with K-ras mutations had no significant changes in overall survival or in progression-free survival. Those without the mutations, on the other hand, appeared to benefit significantly from the therapy.

People with no K-ras mutations who were treated with cetuximab had nearly twice the overall survival rate compared to the supportive care group -- 9.5 months versus 4.8 months. And, the time of progression-free survival was also nearly doubled for those treated with cetuximab -- 3.7 months versus 1.9 months in the supportive care group.

"Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab," the researchers concluded.

"This study suggests that if someone has this particular mutation, they won't respond to this drug," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society. "The bottom line is that this study is important and really has the potential to impact how we treat patients with colorectal cancer with this very expensive drug."

He added that other researchers have noted similar results for K-ras mutations in earlier-stage colorectal cancer.

"This is one more refinement on personalized medicine, and we're moving into an age of molecular markers that eventually will guide treatment. If someone has a cancer in the future, that cancer will be analyzed for what kind of cancer it is, and then we'll know what the best treatments are for that cancer," Lichtenfeld said.

Another important molecular marker that guides treatment is already in use for breast cancer treatment, according to Lichtenfeld. Breast cancers are tested for a type of receptor called HER2. Those with this molecular marker are likely to have a more aggressive type cancer, but also a type of cancer that responds to treatment with the drug trastuzumab (Herceptin), he said.

"I'm excited about the future, and this study shows we can be more targeted with our targeted therapies," said Lichtenfeld.

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