BACKGROUND: The BRAF V600E mutation and deficiency in mismatch repair status (dMMR) proteins are key biomarkers with both predictive and prognostic implications in CRC. The objective of this study was to assess the impact of both BRAF status and MSI-H status on overall survival (OS) in BRAF-V600E mutated (BRAF-m) and BRAF wild type (BRAF-wt) mCRC patients (pts) using real-world data. METHODS: A retrospective analysis of adult mCRC pts diagnosed between Apr 2013-Nov 2020 was conducted using the Flatiron Health database. Pts were stratified by BRAF V600E mutation status (BRAF-m or BRAF-wt) and further categorized into MSI-H and MSS. Propensity scores were used to match pts 1:1 within study groups based on demographics and disease characteristics, such as age, sex, race, Charlson Comorbidity Index, insurance type, practice type and region. Kaplan-Meier analyses were used to assess OS and Log-Rank tests were used to determine differences in overall survival between BRAF-m vs BRAF-wt pts overall and within each BRAF cohort between MSI-H and MSS pts. RESULTS: Of the 3,635 pts that met eligibility criteria, 442 (12%) were BRAF-m and 3,193 (88%) were BRAF-wt. Mean age was 62 years. Most pts were white (N=2,400, 66%) and male (N=2,106, 58%). BRAF-wt matched controls were identified for the 442 BRAF-m patients. Median OS in the overall population was significantly shorter for BRAF-m pts compared to BRAF-wt pts (14 vs 36 months (mos), respectively; p <0.001). This finding persisted for the matched cohorts (14 vs. 32 mos, respectively; p <0.001). 97 and 105 pts were MSI-H in the BRAF-m and BRAF-wt cohorts, respectively. Among BRAF-m pts, pre-matching median OS for MSI-H and MSS pts was 11 vs 14 mos (p =0.500) and post-matching: 12 vs 14 mos (p =0.770). Among BRAF-wt pts, pre-matching median OS for MSI-H and MSS pts was 24 vs 36 mos (p =0.034) and post-matching: 24 vs 33 mos (p =0.899). CONCLUSION: Consistent with prior studies, we found that pts with BRAF-m mCRC had significantly shorter survival compared to patients with BRAF-wt. MSI-H status was not found to have a statistically significant impact on median OS in BRAF-m or BRAF-wt pts. Limitations of this study include potential non- generalizability of the conclusions based on a specific data source and the relative small sample size of the BRAF-m cohort.
EPR22-117: Evaluation of the Influence of the BRAF V600E Mutation and of the Microsatellite Instability on the Overall Survival (OS) of Metastatic CRC Patients Based on Real World Data
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