Clinical Impact of Primary Tumor Location and RAS, BRAF V600E, and PIK3CA Mutations on Epidermal Growth Factor Receptor Inhibitor Efficacy as Third-line Chemotherapy for Metastatic Colorectal Cancer.

Abstract

Primary tumor location and RAS and BRAF V600E mutations are predictors of the efficacy of epidermal growth factor receptor (EGFR) inhibitors. However, there are limited reports on their effects on the outcomes of third-line chemotherapy with EGFR inhibitors in metastatic colorectal cancer (mCRC) patients. We retrospectively collected the clinical data of KRAS exon 2 wild type (WT) mCRC patients treated with EGFR inhibitor monotherapy or EGFR inhibitor plus irinotecan as third-line chemotherapy. The association between primary tumor location, RAS (KRAS exon 3, 4 or NRAS), BRAF V600E, and PIK3CA mutational status, and treatment outcome was evaluated. A total of 72 patients were included in this study. In multivariate analysis, RAS (p=0.004) and BRAF mutations (p=0.00008) were independent factors for shorter PFS. Poor performance status (p=0.01) and BRAF mutation (p=0.00002) were independent factors for shorter OS, whereas primary tumor location and PIK3CA mutation did not influence survival. Additional analysis of RAS and BRAF mutations could contribute to the selection of patients who are likely to benefit from third-line EGFR inhibitors, regardless of primary tumor location.