ASCO Supports KRAS Testing Before Anti-EGFR Therapy

Roxanne Nelson

January 15, 2009

January 15, 2009 — The American Society of Clinical Oncology (ASCO) released its first Provisional Clinical Opinion (PCO) on the use of KRAS gene mutation testing in patients with metastatic colorectal cancer, in support of testing before treatment is initiated. The release of the opinion coincides with the 2009 Gastrointestinal Cancers Symposium, being held in San Francisco, California, and is intended to guide the use of the epidermal growth-factor receptor (EGFR) inhibitors cetuximab (Erbitux) and panitumumab (Vectibix).

The PCO states that, "based on systematic reviews of the relevant literature, all patients with metastatic colorectal carcinoma who are candidates for anti-EGFR antibody therapy should have their tumor tested for KRAS mutations in a Clinical Laboratory Improvement Amendments (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 issued its opinion based on compelling data from phase 2 and 3 clinical trials that demonstrated that the anti-EGFR monoclonal antibodies cetuximab and panitumumab could benefit patients with metastatic colorectal cancer. However, subsequent retrospective subset analyses of the trial data strongly suggested that these therapies are not beneficial in patients with KRAS mutations detected in codon 12 or 13.

"Personalized medicine is the next frontier in cancer care. Basing cancer treatment on the unique genetic characteristics of the tumor or the individual with cancer will improve patient outcomes and help avoid unnecessary costs and side effects for patients who are unlikely to benefit," said Richard L. Schilsky, MD, ASCO president and professor of medicine at the University of Chicago Medical Center, in Illinois, in a statement. "Using KRAS testing to guide colorectal cancer treatment is a prime example of where cancer care is heading."

To date, 5 randomized controlled trials have evaluated the efficacy of cetuximab or panitumumab, among patients with metastatic colorectal carcinoma, in relation to KRAS mutational status. In addition, 5 single-group trials have retrospectively evaluated tumor response according to KRAS status.

An economic analysis presented at the Gastrointestinal Cancers Symposium, which is cosponsored by ASCO, found that upfront testing for KRAS status and limiting anti-EGFR therapy to patients with wild-type KRAS tumors can result in drug cost savings of $604 million for cetuximab alone, according to lead author Veena Shankaran, MD, from the Northwestern University Feinberg School of Medicine, in Chicago.

"Although it is not yet reflected in pharmaceutical labeling, practice guidelines and clinical trials have incorporated KRAS testing as a standard procedure prior to cetuximab use," said Dr. Shankaran during a press briefing.

Testing for KRAS gene mutations was recently added to the National Comprehensive Cancer Network's updated clinical practice guidelines for colon cancer, as reported by Medscape Oncology.


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