BRAF-Mutated Colorectal Cancer: What Is the Optimal Strategy for Treatment?

  • Romain Cohen
  • Pascale Cervera
  • Magali Svrcek
  • Anna Pellat
  • Chantal Dreyer
  • Aimery de Gramont
  • Thierry André
Lower Gastrointestinal Cancers (AB Benson, Section Editor)
First Online:
Part of the following topical collections:
  1. Topical Collection on Lower Gastrointestinal Cancers

Opinion statement

The BRAF activating mutation, harbored by approximately 10% of colorectal cancers (CRC), confers dramatic prognosis to advanced diseases. In early-stage setting, the identification of the BRAF mutation does not impact the therapeutic decision. Yet, the BRAF mutation could be considered as a stratification factor in adjuvant trials, because of its prognostic impact after relapse. Moreover, both BRAF mutation and mismatch repair (MMR) statuses should be determined in all CRC to help identify sporadic tumors versus Lynch syndrome-related tumors. Indeed, in patients with MMR-deficient (dMMR) tumors and MLH1 loss of expression, the BRAFV600E mutation indicates a sporadic origin. In advanced BRAF-mutated CRC, the standard of care remains fluoropyrimidine-based cytotoxic regimen in combination with bevacizumab. Although a recent meta-analysis showed that there was insufficient data to justify the exclusion of anti-EGFR monoclonal antibodies, antiangiogenic agents should be preferred in the first-line setting. Despite the lack of a randomized phase 3 study dedicated to BRAF-mutated CRC, chemotherapy intensification combining a quadruple association of 5-fluorouracil, oxaliplatin, irinotecan (FOLFOXIRI), and bevacizumab seems like a valid option. Although first results with BRAF inhibitors as single agents in BRAF-mutated CRC were disappointing, their association with therapies targeting the MAPK pathway seems to overcome the primary resistance to BRAF inhibition. In the field of sporadic CRC, the BRAF mutation is strongly associated with MMR deficiency. Considering breakthrough results of immune checkpoint inhibitors in dMMR repair tumors, determination of the MMR status appears to be mandatory. Given the dramatic prognosis conferred by the BRAF mutation, patients with BRAF-mutated advanced CRC need to be systematically identified and proposed for clinical trial enrolment in order to benefit from innovative therapies.

Keywords

BRAFV600E Colorectal cancer Microsatellite instability Checkpoint inhibitor Vemurafenib Dabrafenib FOLFOXIRI 
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Notes

Compliance with Ethical Standards

Conflict of Interest

Romain Cohen declares that he has no conflict of interest.

Pascale Cervera declares that he has no conflict of interest.

Magali Svrcek declares that she has no conflict of interest.

Anna Pellat declares that she has no conflict of interest.

Chantal Dreyer declares that she has no conflict of interest.

Aimery de Gramont has received compensation from Roche for service as a consultant and non-financial research support from Sanofi.

Thierry André has received compensation from Roche and Amgen for service as a consultant, as well as honoraria from Baxter, Bayer, Bristol-Myers Squibb, Lilly, MSD, Merck Serono, Novartis, Sanofi, and Servier.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Romain Cohen
    • 1
  • Pascale Cervera
    • 2
  • Magali Svrcek
    • 2
  • Anna Pellat
    • 1
  • Chantal Dreyer
    • 1
  • Aimery de Gramont
    • 3
    • 4
  • Thierry André
    • 1
    • 4
  1. 1.Department of Medical OncologySaint-Antoine HospitalParisFrance
  2. 2.Department of PathologySaint-Antoine HospitalParisFrance
  3. 3.Department of Medical OncologyInstitut Hospitalier Franco-BritanniqueLevallois-PerretFrance
  4. 4.GERCOR, Oncology Multidisciplinary GroupParisFrance

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