PREDICTING RESPONSE TO EGFR INHIBITORS

Predicting Nonresponse to Colorectal Cancer Treatment

More than 140,000 people in the United States are diagnosed with colorectal cancer (CRC) each year, and about 28,000 of these cases are metastatic CRC (mCRC). Despite options for targeted chemotherapy, people diagnosed with mCRC survive a median of only about 2 years. Among available treatment options are monoclonal antibody-based agents, such as cetuximab and panitumumab, which are directed against epidermal growth factor receptor (EGFR) when it is displayed on tumor cell surfaces. Whereas most cases of CRC involve tumor cells displaying EGFR, only about 10% of patients respond to treatment with cetuximab or panitumumab. Identification of genetic variants that could make patients unlikely to respond, before these therapies are initiated, could help to avoid potential side effects from ineffective treatment and to avoid losing time that might have been spent using other, potentially effective treatment options.^[1]

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (EWG) recently released a recommendation statement addressing commonly tested KRAS variants. The EGAPP recommendation also considered testing for BRAF V600E, NRAS, and PIK3CA mutations, as well as for loss of PTEN and AKT protein expression. They recommended using KRAS mutation analysis, but found insufficient evidence to recommend for or against the other tests, when cetuximab or panitumumab are being considered for use in patients with mCRC.^[1]