Authors' objectives:

This Assessment evaluates and summarizes the evidence of using tumor cell KRAS mutational status as a predictor of nonresponse to EGFR-targeted therapy with monoclonal antibodies cetuximab and panitumumab in patients with metastatic colorectal cancer.

Authors' recommendations: The data show that the clinical benefit of using EGFR inhibitors in treating metastatic colorectal cancer, either as monotherapy or in combination with other treatment regimens, is not seen in patients with KRAS-mutated tumors. These data support knowing a patient’s tumor mutation status before consideration of use of an EGFR inhibitor in the treatment regimen. Identifying patients whose tumors express mutated KRAS will avoid exposing patients to ineffective drugs, avoid exposure to unnecessary drug toxicities, and expedite the use of the best available alternative therapy. Based on the available evidence, the Blue Cross and Blue Shield Association Medical Advisory Panel made the following judgments about whether use of KRAS mutation analysis to predict nonresponse to anti-EGFR monoclonal antibodies cetuximab and panitumumab to treat metastatic colorectal cancer meets the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria. 1. The technology must have final approval from the appropriate governmental regulatory bodies. KRAS mutation analysis using PCR methodology is commercially available as a laboratory-developed test. Such tests are regulated under the Clinical Laboratory Improvement Amendments (CLIA). Premarket approval from the FDA is not required when the assay is performed in a laboratory that is licensed by CLIA for high-complexity testing. 2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes. The evidence compiled from 5 randomized trials and 5 single-arm studies is sufficient to conclude that patients with mutated KRAS tumors in the setting of metastatic colorectal cancer do not respond to anti-EGFR monoclonal antibody therapy, do not derive survival benefit, and may experience decreased progression-free survival. 3. The technology must improve the net health outcome; and4. The technology must be as beneficial as any established alternatives. There is sufficient evidence to permit conclusions regarding the use of KRAS mutation analysis when the use of an EGFR inhibitor is a consideration in the management of a patient with metastatic colorectal cancer. 5. The improvement must be attainable outside the investigational settings. The improvement in health outcomes in testing for a KRAS mutation in a patient with metastatic colorectal cancer prior to treatment with an anti-EGFR monoclonal antibody can be attained outside of the investigational setting. Based on the above, use of KRAS mutation analysis to predict nonresponse to the anti-EGFR mono clonal antibodies cetuximab and panitumumab to treat metastatic colorectal cancer meets the TEC criteria.

Project Status: Completed

URL for project: http://www.bcbs.com/blueresources/tec/vols/23/kras-mutations.html

Year Published: 2008

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: BlueCross BlueShield Association

Contact Address: BlueCross BlueShield Association, Technology Evaluation Center, 225 North Michigan Ave, Chicago, Illinois, USA. Tel: 888 832 4321

Contact Name: tec@bcbsa.com

Contact Email: tec@bcbsa.com

Copyright: BlueCross BlueShield Association (BCBS)