Incidence of mutations in mCRC patients

ESMO guidelines recommend that 'BRAF mutation status should be assessed simultaneously with the evaluation of RAS, for prognostic assessment and for the option of treatment with cetuximab-encorafenib'6





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Why test?6

  • Adhere to ESMO guideline recommendations, which base the use of cytotoxics and biologicals on molecular profile
  • Gain a deeper knowledge of the impact and clinical relevance of mutations
  • Promote enrolment of patients into clinical trials with new targeted approaches
  • Improve outcomes for patients with mCRC

Molecular heterogeneity of colorectal cancer is substantial

The MAPK pathway is the most frequently dysregulated signalling pathway linked to various cancers, such as colorectal cancer. Key drivers for the aberrant MAPK signalling are mutations in the downstream pathway components RAS or BRAF.1,2

Created from Refs. 1, 2
EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; MAPK, mitogen-activated protein kinase; MEK, MAPK/ERK kinase.

Patients with mCRC with RAS- or BRAF-mutated tumours may have poorer outcomes than those with wild-type tumours

RAS- and, to a greater extent, BRAF-mutated tumours may be associated with a poorer prognosis than RAS and BRAF wild-type tumours, based on retrospective analyses of clinical trial data3-5

Overall survival according to molecular subgroups in 357 patients with mCRC receiving first-line treatment3

Adapted from the TRIBE study: Ref. 3
According to the study protocol, the mutation status of KRAS codons 12, 13, and 61 and of BRAF codon 600 was assessed


1 Santarpia L, et al. Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy. Expert Opin Ther Targets 2012;16:103–19
2 Liu F, et al. Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy. Acta Pharm Sin B 2018;8: 552–62
3 Cremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study Lancet Oncol. 2015;16(13):1306–15.
4 Stintzing S, et al. Impact of BRAF and RAS mutations on first-line efficacy of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab: analysis of the FIRE-3 (AIO KRK-0306) study Eur J Cancer 2017;79:50–60.
5 Peeters M, et al. Updated analysis of KRAS/NRAS and BRAF mutations in study 20050181 of panitumumab (pmab) plus FOLFIRI for second-line treatment (tx) of metastatic colorectal cancer (mCRC). Journal of Clinical Oncology 32, no. 15_suppl (May 20, 2014) 3568-3568. DOI: 10.1200/jco.2014.32.15_suppl.3568
6 Cervantes et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023 Jan;34(1):10-32.
7 Tabernero et al. Unmet Medical Need in Patients with Metastatic Colorectal Cancer with BRAF V600E Mutations: A Review. EMJ Oncol. 2020;8[Suppl 3]:2-14
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