A Systematic Literature Review and Meta-Analysis Describing the Prevalence of , and Gene Mutations in Metastatic Colorectal Cancer.

Background: Tumors of the metastatic colorectal cancer (mCRC) patients that are wildtype (WT) for or mutations respond more favorably to anti-epidermal growth factor receptor (EGFR) treatments. Treatment guidelines now recommend that all mCRC patients have WT and tumor status confirmed prior to initiating anti-EGFR therapy. Evidence also suggests that mutations may predict lack of response to anti-EGFR therapy. As such, there is now a need for comprehensive data on the prevalence of , , and mutations among patients with mCRC.

Methods: A systematic literature review was conducted among studies that described the prevalence of , , and gene mutations in mCRC patients. Observational cohort studies and standard of care arm of randomized clinical trials were included. Random effects meta-analysis models were used to create summary prevalence estimates for each of the mutation types. Subgroup analyses were also conducted to identify potential sources of heterogeneity. Exploratory analyses of overall and progression-free survival by mutation status were also conducted.

Results: This systematic review and meta-analysis included 275 studies comprising 77,104 mCRC patients. The summary prevalence estimate was 35.9% for mutations, 7.1% for mutations, and 4.1% for mutations. Female patients had significantly more and mutations than males, and significant variation by study location was observed for both and mutation prevalence. Overall survival was significantly decreased for patients with , , and mutations compared to those with WT tumors. Progression-free survival was also significantly decreased among patients with and mutations.

Conclusions: , , and mutation statuses in patients with mCRC are important predictors of treatment success and may also have prognostic value. In this paper we present the first systematic and comprehensive literature review and meta-analysis of the prevalence of , , and mutations and demonstrate the prognostic impact of mutation status on survival.