Non–V600 BRAF Mutations in Metastatic Colorectal Cancer


Key Points

  • In patients with metastatic colorectal cancer, non–V600 BRAF mutations were found in 2.2% of cases.
  • Non–V600 BRAF–mutant disease was associated with better overall survival than V600E BRAF–mutant disease or BRAF wild-type disease.

As reported by Jones et al in the Journal of Clinical Oncology, BRAF mutations occurring outside of codon 600 are found in a small proportion of cases of metastatic colorectal cancer and are associated with improved clinical outcome.

Study Details

The retrospective cohort study involved 9,643 patients with metastatic colorectal cancer who had undergone next-generation sequencing testing at three large molecular genetics reference laboratories. Of them, 208 patients (2.2%) had non–V600 BRAF mutations, with such mutations accounting for 22% of all BRAF mutations identified.

Associations and Outcome

Compared with cases with V600 BRAF mutations, those with non–V600 BRAF mutations were younger (median = 58 vs 68 years), less likely to be female (46% vs 65%), and had fewer high-grade tumors (13% vs 64%) or right-sided primary tumors (36% vs 81%). Median overall survival was 60.7 months in patients with non–V600 BRAF mutant disease vs 11.4 months in those with V600E BRAF–mutant disease and 43.0 months in those with wild-type BRAF disease (overall P < .001). On multivariable analysis, non–V600 BRAF mutation status was significantly associated with improved overall survival (hazard ratio = 0.18, P < .001).

The investigators concluded: “Non-V600BRAF mutations occur in approximately 2.2% of patients with metastatic [colorectal cancer] and define a clinically distinct subtype of [colorectal cancer] with an excellent prognosis.”

The study was supported by a Clinical and Translational Science Award grant from the National Center for Advancing Translational Science.

Axel Grothey, MD, of Mayo Clinic, Rochester, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.