Patients with advanced colorectal cancer benefit from panitumumab only if they have the normal form of the KRAS gene in their tumors rather than a mutation, according to a presentation at the 2008 Gastrointestinal Cancers Symposium.

KRAS mutations are found in 30 to 50 percent of colorectal cancer patients in the U.S.A. Panitumumab is a fully human monoclonal antibody that blocks epidermal growth factor receptor (EGFR) approved by the Food and Drug Administration as a single agent for treating metastatic colorectal cancer in patients who have not responded to standard chemotherapy.

Earlier retrospective research suggested that KRAS status was an indicator of response to treatment with anti-EGFR antibodies, but definitive conclusions could not be drawn from these studies because they did not include a control group of patients who did not receive antibody treatment.

The Phase III study included 427 patients whose KRAS status was known; 43 percent had a mutation in KRAS. All patients had metastatic colorectal cancer and had exhausted all other treatment options. Patients were randomized to receive best supportive care (palliative care with no anti-cancer agents) or best supportive care plus panitumumab every two weeks.

For patients who received panitumumab, median progression-free survival was 12.3 weeks for the normal KRAS gene versus 7.4 weeks for the mutation. In the best supportive care group, median progression-free survival was 7.3 weeks regardless of KRAS status.

Among patients with normal KRAS who received panitumumab, 17 percent responded to the drug and 34 percent had stable disease. Among patients with a mutation who received panitumumab, tumors did not shrink in any patient and only 12 percent of patients had stable disease.

The majority of side effects from the drug were skin rashes, the most common side effect of all EGFR inhibitors. Skin-related toxicity was reversible upon discontinuation of treatment. Side effects from panitumumab overall did not differ between the two groups (93 percent in the normal KRAS group versus 90 percent in the mutation group), but more severe (grades 3 and 4) side effects were more common in the normal KRAS group (25 percent versus 13 percent in the group with mutated KRAS).

This difference could be due in part to the fact that patients with normal KRAS on panitumumab received on average twice as much of the drug as patients with a mutation because they remained on the treatment longer due to positive response and longer time to progression of their disease.

"By testing for KRAS mutations, physicians may now be able to identify which patients will most likely benefit from panitumumab treatment and potentially avoid unnecessary side effects in those who are unlikely to respond," said lead author, Rafael Amado, MD, executive director in the oncology therapeutic area at Amgen, which manufactures and markets the drug.