Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta-analysis

Studies have shown that the prevalence of RAS and BRAF mutations may differ by tumor sidedness among metastatic colorectal cancer (mCRC) patients. Both mutation status and tumor sidedness may impact survival and disease progression and RAS mutation status has been shown to predict response to anti-epidermal growth factor receptor (EGFR) therapy. A systematic literature review and meta-analysis were conducted to estimate the pooled prevalence of RAS and BRAF mutations by tumor sidedness in studies of mCRC patients. Forty-four studies comprising 15 981 mCRC patients tested for RAS and/or BRAF mutations were included in the meta-analyses. The prevalence of RAS mutations differed significantly by tumor side (32.4% among left-sided tumors, 41.3% among right-sided tumors; P = .017), as did the prevalence of KRAS mutations (35.8% among left-sided tumors, 46.3% among right-sided tumors; P < .0001) and BRAF mutations (4.3% among left-sided tumors, 16.3% among right-sided tumors; P < .0001). Among right-sided tumors, the prevalence of RAS and KRAS mutations varied significantly by study design, with higher prevalence among observational studies than clinical trials, and there was significant variation by study location for the prevalence of KRAS mutations in left-sided tumors and the prevalence of BRAF mutations in right-sided tumors. These results help to better characterize the mCRC population to better inform clinicians and researchers. Few of the included studies reported overall or progression-free survival (PFS) by both tumor sidedness and mutation status. As both of these factors may have prognostic impact, future studies should consider evaluating survival by these variables.