OBJECTIVES: BRAF V600E and microsatellite instability (MSI) are two key biomarkers in metastatic colorectal cancer (mCRC). Around 30% of patients who harbor a BRAF V600E mutation are found to be MSI-high (MSI-H). Using real-world-data, this study compared overall survival (OS) by BRAF V600E status and further stratified by MSI status.

METHODS: A retrospective analysis using the Flatiron Health database was conducted assessing adult mCRC patients diagnosed between April 2013-November 2020. Patients were categorized by BRAF status, BRAF-mutant (m) or BRAF-wild type (wt) and further stratified by MSI status, MSI-H and microsatellite stable (MSS). Patients were propensity score-matched 1:1 within study groups on age, sex, race, Charlson Comorbidity Index, insurance type, practice type and region. The differences in OS between BRAF-m vs BRAF-wt patients, and within each sub-cohort (MSI-H vs. MSS), were assessed using Cox proportional hazard ratio model.

RESULTS: The eligibility criteria were met by 3,635 patients, of which 442 (12.2%) were BRAF-m and 3,193 (87.8%) were BRAF-wt. Mean age was 62 years. Most patients were white (N=2,400, 66.0%) and male (N=2,106, 57.9%). BRAF-wt matched controls were identified for the 442 BRAF-m patients. Overall, the BRAF-m patients had a 2.38-fold (95% CI: 1.96, 2.88; p<0.001) increased death hazard compared to BRAF-wt patients. In both the BRAF-m and BRAF-wt sub-cohorts, MSI-H patients did not have a significant difference in death hazard compared to MSS patients (BRAF-m sub-cohort: 1.06 [95% CI: 0.71, 1.58], p= 0.7597; BRAF-wt sub-cohort: 1.14 [95% CI: 0.71, 1.82]; p=0.5885).

CONCLUSIONS: We found that BRAF-m mCRC patients had a significantly higher death risk compared to BRAF-wt patients, consistent with prior studies. Within both BRAF cohorts, MSI status did not affect mortality. Limitations of this study include potential non-generalizability of the conclusions based on a specific data source and the relatively small sample size of the BRAF-m cohort.