Abstract
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.
Highlights
20% of new colorectal cancer (CRC) cases are metastatic at diagnosis and another 20% of cases progress to metastatic disease.[1,2] RAS mutations have been associated with a lack of response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies used in metastatic colorectal cancer (mCRC) treatment such as cetuximab and panitumumab.[3,4] The American Society for Clinical Oncology recommends that all mCRC patients who are candidates for anti-EGFR therapies should first be tested for the Kirsten RAS (KRAS) mutation.[4]
RAS mutations have been associated with a lack of response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies used in mCRC treatment such as cetuximab and panitumumab.[3,4]
The 44 included studies comprised 15 981 mCRC patients tested for RAS and/or b-type Raf proto-oncogene (BRAF) mutations
Summary
20% of new colorectal cancer (CRC) cases are metastatic (mCRC) at diagnosis and another 20% of cases progress to metastatic disease.[1,2] RAS mutations have been associated with a lack of response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies used in mCRC treatment such as cetuximab and panitumumab.[3,4] The American Society for Clinical Oncology recommends that all mCRC patients who are candidates for anti-EGFR therapies should first be tested for the Kirsten RAS (KRAS) mutation.[4] The requirement to establish RAS status prior to administration of an EGFR has increased the need for more information on the epidemiologic and tumor characteristics by RAS status. A recent pooled analysis of randomized controlled trials of mCRC patients reported significant differences in RAS mutation prevalence estimates by clinical trial, sex, and by country.[5]. Progression-free survival (PFS) has been shown to be significantly improved among patients with wild-type KRAS left-sided tumors who were treated with cetuximab compared to best supportive care (median survival was 5.4 months vs 1.8 months, respectively).[6]
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