A new provisional clinical opinion (PCO) by the American Society of Clinical Oncology (ASCO) recommends that patients with metastatic colorectal cancer (cancer that has spread to other areas of the body) receive testing for mutations in the KRAS (pronounced kay-rass) gene. The test helps predict whether patients will benefit from treatment with drugs that block the epidermal growth factor receptor (EGFR). To learn more about PCOs and what this recommendation means for patients, Cancer.Net talked with Richard L. Schilsky, MD.

Q: What is a provisional clinical opinion and why did ASCO create this tool?

A: The provisional clinical opinion (PCO) is intended to offer timely clinical direction to oncologists (doctors who treat people with cancer) following publication or presentation of potentially practice-changing data from major studies. The PCO is based on rigorous examination of published data by a group of experts who formulate an expert opinion to help guide clinical practice. ASCO created this tool to react to rapidly emerging data that doctors and patients need to consider in making clinical decisions.

Q: What is the KRAS gene and how does it affect the treatment of colorectal cancer?

A: The KRAS gene helps regulate the flow of information inside cells and, when “turned on” by a mutation, leads to uncontrolled cell growth and division. Think of it as the accelerator of your car getting stuck on the floor. KRAS is present in normal as well as tumor cells, but is only mutated in 30% to 40% of colon tumors. In these patients, the tumor is resistant to treatment with the drugs cetuximab (Erbitux) and panitumumab (Vectibix) that block EGFR on the surface of the tumor cells. The reason these drugs don’t work in these patients is that the mutated KRAS gene essentially bypasses the blockade of EGFR and keeps stimulating growth of the tumor.

Q: What does ASCO recommend in its first PCO on KRAS testing for colorectal cancer?

A: ASCO recommends that all patients with metastatic colorectal cancer whose doctors are considering treatment with cetuximab or panitumumab should have their tumor tested for KRAS mutations in an accredited laboratory. If KRAS mutations are detected, then patients should not receive cetuximab or panitumumab as part of their treatment.

Q: What should patients know about this recommendation?

A: This recommendation is based on review of 10 different studies conducted by the Blue Cross and Blue Shield Association’s Technology Evaluation Center in addition to the assessment of an expert panel of oncologists and pathologists assembled by ASCO. Patients should ask their oncologist if treatment with cetuximab or panitumumab is appropriate for them. If so, patients should ask their doctor to arrange for their tumor to be tested for KRAS mutations. This can be done on tissue samples from the patient’s initial surgery and generally does not require another biopsy or procedure. It may take one to two weeks to receive the test results.

Q: What other questions should patients with colorectal cancer ask their doctors about KRAS testing?

A: Patients should also ask their doctors the following questions:

• How likely is it that my tumor has a KRAS mutation?
  
  
• What are my treatment options if the KRAS test shows that my tumor has a mutation?
  
  
• What are my treatment options if the KRAS test is normal?
  
  
• How reliable is the test?
  
  
• Is there any chance that cetuximab or panitumumab will help me even if the test shows a mutation?

Q: Is there anything else to add?

A: KRAS testing is a new strategy that represents a step toward personalized medicine. The goal is to select the best treatment for each patient based on the unique features of each person’s tumor.

Dr. Schilsky is Professor of Medicine at the University of Chicago and Chairman of the Cancer and Leukemia Group B, a national clinical research group sponsored by the National Cancer Institute. Dr. Schilsky is the 2008-2009 ASCO President.

More Information

Cancer.Net Guide to Colorectal Cancer

Latest News on Colorectal, Esophageal, and Pancreatic Cancers from the 2009 Gastrointestinal Cancers Symposium

Last Updated: March 30, 2009