Margonis GA, et al. - In patients with metastatic colorectal liver cancer, researchers investigated the prognostic association of BRAF mutations with survival and recurrence independently and compared with other prognostic determinants, such as KRAS mutations. They noted worse prognosis and increased risk of recurrence in association with the presence of the V600E BRAF mutation. The V600E mutation was identified to be a stronger prognostic factor than KRAS and also was the strongest prognostic determinant in the overall cohort.

Methods

• Researchers performed a cohort study comprising all patients who underwent resection for CRLM with curative intent from January 1, 2000, through December 31, 2016, at the institutions participating in the International Genetic Consortium for Colorectal Liver Metastasis and had data on BRAF and KRAS mutational status.
• They used multivariate Cox proportional hazards regression models to ascertain long-term outcomes.
• Hepatectomy was performed as an intervention in patients with CRLM.
• They assessed the association of V600E and non-V600E BRAF mutations with disease-free survival (DFS) and overall survival (OS) as the main outcomes and measures.

Results

• Inclusion criteria was met by 853 patients (510 men [59.8%] and 343 women [40.2%]; mean [SD] age, 60.2 [12.4] years); of these, 849 were included in the study analyses.
• A mutated (mut) BRAF/wild-type (wt) KRAS (V600E and non-V600E) genotype was identified in 43 (5.1%) patients; a wtBRAF/wtKRAS genotype in 480 (56.5%) patients; and a wtBRAF/mutKRAS genotype in 326 (38.4%) patients .
• Observations revealed that compared with the wtBRAF/wtKRAS genotype group, patients with a mutBRAF/wtKRAS genotype more frequently were female (27 [62.8%] vs 169 [35.2%]) and 65 years or older (22 [51.2%] vs 176 [36.9%]), had right-sided primary tumors (27 [62.8%] vs 83 [17.4%]), and presented with a metachronous liver metastasis (28 [64.3%] vs 229 [46.8%]).
• Multivariable analysis suggested that V600E but not non-V600E BRAF mutation was correlated with worse OS (hazard ratio [HR], 2.76; 95% CI, 1.74-4.37; P < .001) and DFS (HR, 2.04; 95% CI, 1.30-3.20; P=.002).
• The V600E BRAF mutation vs the KRAS mutations demonstrated a stronger association with OS and DFS (β for OS, 10.15 vs 2.94; β for DFS, 7.14 vs 2.27).