Test mCRC Patients for KRAS Status

In a decision likely to affect oncology practice nationwide, the American Society of Clinical Oncology (ASCO) is recommending clinicians order KRAS gene mutation testing for all patients with a diagnosis of metastatic colorectal cancer (mCRC) prior to establishing a treatment plan. ASCO released the “Provisional Clinical Opinion” ahead of the 2009 Gastrointestinal (GI) Cancers Symposium on January 15-19, 2009. Several studies at the symposium provided new evidence that treatment with the anti-EGFR inhibitors cetuximab (Erbitux) and panitumumab (Vectibix) had limited effectiveness in patients with the KRAS mutation. Conversely, the studies found that wild-type KRAS tumors demonstrated strong response to cetuximab and panitumumab. These findings support the need to target patients selectively for these anti-EGFR treatments based on KRAS status.

According to Veena Shankaran, MD, Northwestern University, Chicago, Illinois, and colleagues, at least 35.6% of patients with mCRC have mutated KRAS, and the incidence may be as high as 46%. They calculated that determining the KRAS status of patients with mCRC before treatment could save the healthcare system at least $604 million. This figure represents the cost savings generated from limiting cetuximab and panitumumab treatments to those with wild-type KRAS tumors minus the expense of universal KRAS testing for the estimated 28,724 patients who receive a diagnosis of mCRC annually in the United States. Universal KRAS testing in patients with mCRC would also benefit patients, allowing them to receive a therapeutic intervention more likely to be effective from the outset and sparing them from the toxicities associated with an ineffective treatment. Targeted treatment could result in better rates of PFS and overall survival.

Based on compelling trial results presented at the GI Cancer Symposium, in conjunction with previously published studies, the 9-member ASCO panel stated, “All patients with metastatic colorectal carcinoma who are candidates for anti-EGFR antibody therapy should have their tumor tested for KRAS mutations in a CLIA-accredited laboratory. If KRAS mutation in codon 12 or 13 is detected, then patients with metastatic colorectal carcinoma should not receive anti-EGFR antibody therapy as part of their treatment.” ASCO notes that adherence to the “Provisional Clinical Opinion” is voluntary. The National Comprehensive Cancer Network updated its clinical practice guidelines in 2008 to advise testing patients with colon cancer for KRAS gene mutations.

Eli Lilly, which produces Erbitux in conjunction with Bristol Myers Squibb, and Amgen, the maker of Vectibix, informed FDA regulators in December that recent data showed these monoclonal antibodies were primarily effective in patients with a wild-type KRAS gene. They have requested the FDA’s permission to modify labeling of the drugs to inform physicians not to use them to treat patients with mCRC who have mutant KRAS. Many cancer treatment centers and private practices are not waiting for the FDA decision and have already begun testing their patients with mCRC for KRAS status.