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Background:   BRAF  mutations portend a poor prognosis in metastatic colorectal cancer (mCRC). Whether these patients may benefit from more aggressive frontline chemotherapy with a triplet regimen such as FOLFOXIRI remains unclear. We used real-world data from a cohort of patients in the United States to assess the  BRAF  testing rate, determine the prevalence of FOLFOXIRI use, and compare survival outcomes in mCRC, stratified by  BRAF  mutation status and first-line therapy.  Methods:  A nationwide electronic health record–derived deidentified database was reviewed for patients diagnosed with mCRC between 2013 and 2018. Those with documented  BRAF  mutation testing who received standard first-line therapy were included. Kaplan-Meier estimates with corresponding log-rank tests and Cox proportional hazards modeling compared survival outcomes stratified by  BRAF  status and first-line therapy.  Results:  Of 4,457 included patients, 3,991 (89.5%) had  BRAF  wild-type ( BRAF wt) and 466 (10.5%) had  BRAF -mutated ( BRAF mt) mCRC. Median overall survival (OS) was 15.4 months in the  BRAF mt group versus 28.1 months in the  BRAF wt group (hazard ratio [HR], 0.48; 95% CI, 0.41–0.56;  P &lt;.001). Only 3% of patients with  BRAF  mutations received first-line FOLFOXIRI ± bevacizumab, with a median OS of 13.8 months compared with 15.5 months in those treated with doublet chemotherapy ± bevacizumab ( P =.38). In patients with  BRAF  mutations, propensity-weighted analysis did not detect a significant improvement in OS with FOLFIRI + bevacizumab (HR, 0.90; 95% CI, 0.58–1.39;  P =.63) or FOLFOX/CAPEOX + bevacizumab (HR, 0.81; 95% CI, 0.52–1.26;  P =.35) versus doublet chemotherapy alone. In 2018, only 56% of patients diagnosed with mCRC had documented  BRAF  testing at any time.  Conclusions:  This real-world data analysis confirms the negative prognostic impact of  BRAF  mutations in mCRC and suggests that FOLFOXIRI has not been widely adopted in the United States. The proportion of patients with documented  BRAF  testing in this real-world population was low at 56%. We were unable to show any significant difference in OS of patients with  BRAF mt mCRC based on the first-line therapy received.

Real-World Outcomes of Patients With BRAF-Mutated Metastatic Colorectal Cancer Treated in the United States