June 2, 2008 (Chicago) -- For the first time, doctors have used a molecular test to pinpoint which people with newly diagnosed colorectal cancer are most likely to benefit from the targeted therapy Erbitux.
In the large international study, researchers found that patients with colon cancer who have a normal version of a cancer-associated gene are more likely to respond to initial treatment with Erbitux plus chemotherapy than to chemo alone.
People with a mutated KRAS gene, on the other hand, gained no benefit from Erbitux.
About two-thirds of colon cancer patients have the normal version of the KRAS gene, according to study leader Eric van Cutsem, MD, PhD, of the University Hospital Gasthuisberg in Leuven, Belgium.
Van Cutsem tells WebMD that the test, which is already available, should be routinely performed on colon cancer patients as soon as they are diagnosed.
"That way we can ensure we offer them the best treatment strategies," he says. "If we know in advance that a patient has the mutation, we know that we don't have to treat them with [Erbitux]," van Cutsem says.
He notes that European regulators were so impressed with the results that last week they approved Erbitux -- but only in patients with the normal version of the gene.
The findings were presented at the annual meeting of the American Society of Clinical Oncology (ASCO).
KRAS Predicts Response to Erbitux
Erbitux is a monoclonal antibody that blocks the effects of a protein called epidermal growth factor (EGFR) that fuels tumor growth. It's approved for treating metastatic colorectal as well as certain types of head and neck cancer.
Originally, researchers thought that by testing for EGFR, they could predict which patients would benefit from the targeted drug.
That didn't pan out. Instead, they found that KRAS -- which regulates other proteins downstream in the EGFR signaling pathway -- is a much better predictor of outcome.
For the new analysis, the researchers studied tumor samples from 587 patients with newly diagnosed colorectal cancer that had already spread to other parts of their body.
Among the results:
- People with normal KRAS genes were 32% less likely to have their cancer progress than those who had mutated KRAS genes.
- At one year, 43% of patients with normal KRAS genes given Erbitux and chemo were alive and free of cancer vs. 25% given chemotherapy alone.
"In KRAS-mutant patients, there was no difference [in response rates]," van Cutsem says.
- Tumors shrank by more than half in 59.3% of patients with the normal gene, compared with only 43.2% of those on chemo alone. Again, there was no difference in response rates among those with the KRAS mutation.
- The main side effect, as in other studies of Erbitux, was an acne-like rash. It developed in 16.2% of patients on combo therapy, but in none on chemo alone.
'An Exciting Era'
Julie Gralow, MD, chairwoman of ASCO's communications committee and a cancer specialist at the University of Washington, says, "This is an exciting area of targeted agents."
Noting that therapies like Erbitux typically cost upwards of $5,000, Gralow says, "A big question is, how are we going to be able to afford these drugs in our patients? With KRAS testing, we can predict the two-thirds of patients who will benefit. We don't need to give this drug to the other third now."
That, she says, will spare them both the cost and side effects of unnecessary treatment. Gralow moderated a news conference to discuss the findings.