Concordance of Predictive Markers for EGFR Inhibitors in Primary Tumors and Metastases in Colorectal Cancer: A Review

Abstract Background. Currently, only Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status is used as a decisional marker for epidermal growth factor receptor (EGFR) inhibitor therapy in colorectal cancer (CRC) patients. Concordance of KRAS status between primary tumors and metastases has always been considered to be close to perfect; however, cases of discordance have been reported. The actual rate of concordance of KRAS status remains unclear, as is the same for v-raf murine sarcoma viral oncogene homolog B1 (BRAF), phosphatidylinositol 3-kinase CA subunit (PIK3CA), and loss of phosphatase and tensin homologue deleted on chromosome ten (PTEN). Therefore, it is unknown whether it is necessary to perform mutational analysis on metastases instead of on (or in addition to) primary tumors. Design. A systematic literature search was conducted to collect all studies testing concordance of KRAS in CRC, and also of BRAF, PIK3CA, and loss of PTEN. Results. Twenty-one studies have reported concordance of KRAS, with an overall concordance rate of 93% (range, 76%–100%). Overall concordance rates of studies testing concordance of BRAF status and loss of PTEN were 98% and 68%, respectively. Three studies reported concordance of PIK3CA status (range, 89%–94%). Conclusion. Though discordance of KRAS status does occur, it is uncommon. When considering the downsides of testing metastatic tissue in all patients along with the low incidence of discordance, we conclude that that testing the primary tumor (or whatever tissue available) is sufficient for clinical decision making on EGFR inhibitor therapy.