# Clinical impact of first-line therapeutic strategies in BRAF V600E-mutant metastatic colorectal cancer: real-world evidence and prognostic insight

## TL;DR

This study examines real-world treatment outcomes for BRAF V600E-mutant metastatic colorectal cancer, finding that chemotherapy plus anti-VEGF provides the best survival, while BRAF-targeted therapies show high response rates.

## Contribution

The study provides real-world evidence comparing first-line treatment strategies for BRAF V600E-mutant mCRC, identifying survival and response trends in a clinical cohort.

## Key findings

- Chemotherapy plus anti-VEGF (bevacizumab) showed longest OS (21.2 months) and PFS (10.5 months) in BRAF V600E-mutant mCRC.
- BRAF-targeted therapies achieved the highest ORR (53.8%) and DCR (76.9%) despite shorter survival outcomes.
- Right-sided tumors were unexpectedly associated with improved survival (HR: 0.20).

## Abstract

BRAF V600E-mutant metastatic colorectal cancer (mCRC) is associated with poor prognosis and limited response to standard therapies. Recent clinical trials have explored the benefit of targeted therapies, but real-world data remain limited.

This retrospective study analyzed 36 patients with BRAF V600E-mutant mCRC who received first-line treatment between 2018 and 2024 at Taichung Veterans General Hospital. Patients were grouped by initial regimen: chemotherapy alone, chemotherapy plus anti-VEGF (bevacizumab), or chemotherapy combined with BRAF-targeted ± MEK inhibitors. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included objective response rate (ORR) and disease control rate (DCR).

Mean OS and PFS were longest in patients receiving chemotherapy plus anti-VEGF (21.2 and 10.5 months, respectively), compared to chemotherapy alone (OS 14 months, PFS 7.7 months) and anti-BRAF targeted therapy (OS 13.5 months, PFS 6.5 months). The highest ORR (53.8%) and DCR (76.9%) were observed in patients receiving BRAF-targeted regimens. Multivariate analysis identified liver metastasis and ECOG ≥2 as poor prognostic factors. Unexpectedly, right-sided tumors were associated with improved survival (HR: 0.20, p = 0.028). Subsequent use of BRAF-targeted therapy in some patients may have contributed to extended OS.

In this real-world cohort, chemotherapy combined with anti-VEGF provided the best survival outcomes, while BRAF-targeted strategies showed promising response rates. Liver involvement and poor performance status remained negative prognostic indicators. These findings support a personalized treatment approach and highlight the need for continued prospective validation.