Real-world evaluation of treatment patterns and clinical outcomes in patients with BRAF-V600E metastatic colorectal cancer (mCRC) in Canada

Background: BRAF V600E mutations are identified in 10 % of metastatic colorectal cancer (mCRC) cases. In this project, we evaluated the clinicopathologic features and natural history of patients with BRAF mutant (BRAF-mt) mCRC prior to era of BRAF targeted therapy. Methods: This is a retrospective project evaluating patients with diagnosed with mCRC with an identified BRAF V600E mutation between January 1, 2015 and December 31, 2021 seen at the Ottawa Hospital Cancer Centre prior to the approval of cetuximab and encorafenib in Canada. Demographic, clinical, and cancer characteristics were collected from the medical records. Outcomes of interest included overall survival (OS) and time to next therapy (TNT). Results: 71 patients were included. The median age was 69 years, 37 (52 %) patients were females, and 19 (27 %) were mismatch repair deficient (dMMR). Median OS was 12.9 months with 21 (30 %) patients living greater than 2-years. Signet ring histology (HR=7.27, p G 0.001), peritoneal metastasis (HR=2.29, 0.003), distant lymphatic metastasis (HR=2.70, p G 0.001), brain metastasis (HR=2.86, p G 0.048) and metastatectomy (HR=0.17, p G 0.001) were associated with OS. Forty-six (65 %) patients received first-line systemic therapy, 14 (20 %) second-line and 2 (3 %) third-line. Median duration of therapy was 8.5 months for first-line, 5.5 months for second-line and 1.5 months for third-line. Conclusion: Real world data demonstrates that patients with BRAF-V600E mCRC have poor clinical outcomes with traditional systemic therapies. Only a minority of patients received second-or third-line systemic treatments, highlighting the importance of ongoing research evaluating incorporation of targeted therapy in first-line treatment.