Researchers link gene mutation to Erbitux response

LOS ANGELES (Reuters) - Identifying a gene mutation could reveal which colon cancer patients are likely to benefit from ImClone Systems Inc.'s Erbitux, researchers said on Tuesday.

About 30 percent of all colon cancer patients have a poor response to the drug, said Dr. Pierre Laurent-Puig, a professor of Oncology at University of Paris-Descartes and author of a study linking a mutation in a gene known as KRAS to a poor response to Erbitux.

"Because a variety of different effective agents may now be available for any given type of cancer, deciding which treatment regimen is likely to be the most effective and the least toxic is more complicated than ever," he said.

Erbitux, like Amgen Inc.'s Vectibix, is a biologic drug designed to block a protein called epidermal growth factor (EGF) that cancer cells need to grow.

Dr. Richard Goldberg, chief of hematology, oncology at the University of North Carolina said some patients have a good response to these drugs. "I would rather have a marker that tells me I don't need to treat someone with a drug they are not going to respond to," said Goldberg, who was not involved in the trial.

The French study, involving 114 patients who had been given Erbitux in combination with chemotherapy drug irinotecan, found that almost none of the patients who responded to the drug had an activating KRAS mutation.

By comparison the mutation was found in 35 percent of patients with stable disease and 55 percent of patients with progressive disease, the researchers said.

Laurent-Puig said the KRAS enzyme is a key component in the cascade of molecular interactions that occur after epidermal growth factor meets its receptor, but mutations in the gene could allow the enzyme to function whether or not it receives a signal from the EGF receptor.

As a result, even though Erbitux blocks the receptor, it may not block the molecular signals, he said.

The researchers also found that the KRAS mutations are independent of the skin rash or acne that has come to be associated with a response to Erbitux in some patients.

The results were presented here at the annual meeting of the American Association for Cancer Research.

ImClone sells Erbitux in the United States in partnership with Bristol-Myers Squibb.