The following article features coverage from the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2021. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

New research suggests that BRAF mutant allele fraction (MAF) is an independent prognostic marker associated with survival in patients with BRAF V600E-mutant, metastatic colorectal cancer (mCRC).1

The research was presented at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2021 by Elena Élez, MD, PhD, of Vall d’Hebron University Hospital in Barcelona.

Dr Élez and colleagues previously found evidence to suggest that RAS MAF is a prognostic marker in RAS-mutant mCRC.2 For the current study, the researchers evaluated cell-free DNA BRAF MAF.

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The first aim of this study was to evaluate the contribution of BRAF MAF in a prognostic score for patients with BRAF V600E-mutant mCRC treated with BRAF, EGFR, and/or MEK inhibitors.

There were 40 patients evaluable for this analysis — 14 who had BRAF MAF greater than 5%, 10 with BRAF MAF less than 5%, and 16 with undetectable BRAF MAF.

Dr Élez noted that patients with BRAF MAF greater than 5% had worse performance status, tended to have more tumor sites, and were more likely to have liver metastases.

These patients also had the shortest median overall survival (OS). The median OS was 4.2 months in patients with BRAF MAF greater than 5% (reference), 17.1 months in patients with BRAF MAF below 5%, (hazard ratio [HR], 0.21; P <.001), and 17.5 months in patients with undetectable BRAF MAF (HR, 0.15; P <.001).

In a multivariate analysis, BRAF MAF was significantly associated with OS (HR, 0.48; P = .02), as were performance status (HR, 3.44; P <.001) and neutrophil-to-lymphocyte ratio (HR, 2.74; P =.01).

When the researchers combined clinical features with BRAF MAF, patients could be divided into 3 risk groups that were significantly associated with OS. The median OS was 5.1 months in the high-risk group (reference), 8.4 months in the intermediate-risk group (HR, 0.26; P <.001), and 21.8 months in the low-risk group (HR, 0.05; P <.001).

The second aim for this study was to perform a multi-sequencing analysis to search for potential predictive biomarkers. There were 23 patients included in this analysis.

The results showed that polysomy of chromosome 7 (EGFR, MET, and BRAF) was significantly associated with clinical benefit of BRAF-targeted therapy. In addition, RNF43 somatic mutations were enriched in patients who responded to BRAF inhibitor combinations.

“Our study brings new insights towards the understanding of the underlying molecular landscape of BRAF V600E mutant-associated tumors with sensitivity to BRAF inhibitors and indicates that liquid biopsy is critically needed in future prospective trials for this patient population,” Dr Élez said.

Disclosures: This research was supported by Novartis and others. Dr Élez declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of the ESMO World Congress on Gastrointestinal Cancer 2021 by visiting the conference page.


  1. Élez E, Ros J, Martini G, et al. Integrated analysis of cell-free DNA (cfDNA) BRAF mutant allele fraction (MAF) and whole exome sequencing in BRAFV600E metastatic colorectal cancer (mCRC) treated with BRAF, EGFR +/- MEK inhibitors. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 30-July 3, 2021. Abstract LBA-3.
  2. Élez E, Chianese C, Sanz‐García E, et al. Impact of circulating tumor DNA mutant allele fraction on prognosis in RAS‐mutant metastatic colorectal cancer. Mol Oncol. 2019;13(9):1827–1835. doi:10.1002/1878-0261.12547