What are the ESMO treatment guidelines for metastatic colorectal cancer?

Updated: Mar 18, 2021
  • Author: Elwyn C Cabebe, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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The 2016 European Society for Medical Oncology (ESMO) guidelines for the management of patients with metastatic CRC (mCRC) include the following recommendations on biomarker testing [30] :

  • RAS mutational testing should be carried out on all patients at the time of diagnosis of mCRC , as the presence of RAS mutations is a negative predictive biomarker for response to EGFR antibody therapy for mCRC.
  • RAS testing is mandatory before treatment with the EGFR-targeted monoclonal antibodies cetuximab and panitumumab [I, A].
  • Primary or metastatic colorectal tumor tissue can be used for RAS testing.
  • RAS analysis should include at least KRAS exons 2, 3 and 4 (codons 12, 13, 59, 61, 117 and 146) and NRAS exons 2, 3 and 4 (codons 12, 13, 59, 61 and 117).
  • Tumor BRAF mutation status should be assessed along with RAS mutational status for prognostic assessment (and/or potential selection for clinical trials).
  • Microsatellite instability (MSI) testing in the setting of mCRC can provide helpful information for genetic counselling and has strong predictive value for the use of immune checkpoint inhibitors (eg, pembrolizumab)
  • Dihydropyrimidine dehydrogenase (DPD) testing before fluorouracil (5-FU) administration remains an option but is not routinely recommended; however, it should be done before reintroducing 5-FU in patients who have experienced severe 5-FU toxicity.
  • UGT1A1 phenotyping remains an option for predicting irinotecan toxicity and should be carried out when UGT1A1 deficiency is suspected (on the basis of low conjugated bilirubin levels) and when an irinotecan dose of >180 mg/m 2 per administration is planned.
  • Thymidylate synthase (TS) activity and  TSER genotyping for predicting response to 5-FU are not recommended for use in clinical practice
  • Testing of excision repair cross-complementation group 1 (ERCC1) protein expression for treatment decisions involving the use of oxaliplatin is not recommended outside of clinical trials.

The ESMO guidelines do not recommend the following emerging biomarkers for routine patient management outside of a clinical trial setting:

  • Mutations in PIK3CA, exon 20
  • PTEN loss by IHC
  • Levels of the EGFR ligands amphiregulin, epiregulin and TGF-α
  • Levels of EGFR protein expression
  • EGFR amplification and copy number and EGFR ectodomain mutations
  • HER2 amplification or HER2 activating mutations
  • HER3 and MET receptor overexpression

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