July 24, 2018
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BRAF V600E mutations linked to worse survival in metastatic colorectal cancer

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Harboring a BRAF V600E mutation appeared associated with a poorer prognosis and greater risk for recurrence after curative-intent resection compared with KRAS mutations among patients with colorectal cancer and liver metastasis, according to study results.

Researchers did not observe this association among patients with non-V600E BRAF mutations.

BRAF mutations affect the same signaling pathway as KRAS mutations, the most important difference being that the genetic product of a BRAF-mutated gene exerts its influence downstream from KRAS,” Georgios Antonios Margonis, MD, PhD, surgical oncology fellow at Johns Hopkins University School of Medicine, and colleagues wrote. “Although these similarities suggest a possible role for BRAF as a prognostic indicator of colorectal liver metastasis, this hypothesis has not been well studied because of the low (2%-4%) incidence of BRAF mutations in resected colorectal liver metastasis compared with the 30% to 40% incidence of KRAS mutations.”

Margonis and colleagues assessed 853 patients (59.8% men; mean age, 60.2 years) with colorectal cancer and liver metastasis who underwent resection with curative intent.

All patients had data on BRAF and KRAS mutational status. Researchers observed:

  • 5.1% had mutated BRAF and wild-type KRAS (V600E and non-V600E);
  • 38.4% had wild-type BRAF and mutated KRAS; and
  • 56.5% had wild-type BRAF and wild-type KRAS.

A greater proportion of patients with mutated BRAF and wild-type KRAS were female (62.8% vs. 35.2%), aged 65 years or older (51.2% vs. 36.9%), had right-sided primary tumors (64.3% vs. 46.8%) and presented with a metachronous liver metastasis (64.3% vs. 46.8%) than patients with wild-type BRAF and wild-type KRAS.

Median follow-up was 28.3 months.

BRAF V600E mutations — but not non-V600E BRAF mutations — appeared associated with worse OS (HR = 2.76; 95% CI, 1.74-4.37) and DFS (HR = 2.04; 95% CI, 1.3-3.2).

Researchers observed stronger associations between BRAF V600E mutations and OS and DFS than with KRAS mutations and those endpoints ( for OS, 10.15 vs. 2.94; for DFS, 7.14 vs. 2.27).

“A novel (in surgical colorectal liver metastasis cohorts) finding is that the V600E mutation alone (rather than V600E and non-V600E mutations together) may confer a distinctly aggressive clinical phenotype, thus driving the adverse outcomes associated with BRAF mutation,” the researchers wrote. “However, this finding needs to be interpreted with great caution because of the small number of patients with non-V600E mutations in the cohort.” – by Cassie Homer

Disclosures: The authors report no relevant financial disclosures.