BRAF+ melanoma
What makes it different, makes it vulnerable

When to test for BRAF mutation

Guidelines and algorithms for BRAF testing

Clinical decision-making in melanoma is evolving, as a result of new scientific and clinical trial evidence, and expert scientific discussion. Several guidelines and algorithms for BRAF testing have recently been published, to reflect these evaluations:

  • NCCN Clinical Practice Guidelines in Oncology. Cutaneous melanoma. V3.2019. http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf1
  • Michielin O, et al; ESMO Guidelines Committee. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019 Sep 30 [Epub ahead of print]2
  • Gonzalez D, et al. BRAF mutation testing algorithm for vemurafenib treatment in melanoma: recommendations from an expert panel. Br J Dermatol. 2013;168:700–73
  • Garbe C, et al; European Dermatology Forum (EDF); European Association of Dermato-Oncology (EADO); European Organisation for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline - Update 2016. Eur J Cancer. 2016;63:201–174

There are three points in the patient pathway when testing can be initiated:

When BRAF testing can be triggered Which patients? Who requests the test?
1. Initial diagnosis of melanoma All melanoma patients5 Pathologist (reflex testing)5
2. After initial MDT meeting in the adjuvant setting Patients with high-risk resected melanoma (stage IIC, stage IIIB-IIIC)2 Member of the MDT or pathologist in a ‘reflex manner’ following the initial classification of high-risk disease stage5
3. Advanced melanoma Patients with advanced disease (unresectable stage III or stage IV)2 Clinician (newly acquired sample from metastasis or on primary tumour sample retrieved from archive)2,5

MDT, multidisciplinary team

Reflex testing (option 1 and 2), when the pathologist is directly responsible for requesting the molecular analysis, permits rapid turnaround times, and prevents the need for retrieval of tissue samples at a later date, reducing staff time and therefore cost.5

It is important to note that these guidelines suggest BRAF mutation testing should be carried out in high risk patients or those with metastatic disease.1–3

The ESMO guidelines and NCCN Guidelines® have specific recommendations that are outlined below.1,2

  • ESMO guidelines state that BRAF testing should be2
    • Highly recommended for patients with high-risk resected disease (stage IIC)
    • Mandatory for patients with advanced disease (resectable or unresectable stage III or stage IV)
  • NCCN Guidelines® recommend BRAF testing for patients considered for targeted therapy (in the adjuvant or metastatic setting) or clinical trials1:
    • Patients with stage III melanoma at high risk for recurrence for whom targeted therapy may be an option
    • Patients with stage IV disease or clinical recurrence

This needs to be balanced against unnecessary testing in patients who will, in all likelihood, not need further treatment, or who may need treatment at a later date, when testing for mutations in alternative genes could be required.5

 

  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Cutaneous Melanoma. V.3.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed March 21, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  2. Michielin O, et al; ESMO Guidelines Committee. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019 Sept 30 [Epub ahead of print]. https://www.esmo.org/Guidelines/Melanoma/Cutaneous-Melanoma. Accessed October 16, 2019.
  3. Gonzalez D, et al. BRAF mutation testing algorithm for vemurafenib treatment in melanoma: recommendations from an expert panel. Br J Dermatol. 2013;168:700–7.
  4. Garbe C, et al; European Dermatology Forum (EDF); European Association of Dermato-Oncology (EADO); European Organisation for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline - Update 2016. Eur J Cancer. 2016;63:201–17.
  5. Cree IA, et al; European Society of Pathology Task Force on Quality Assurance in Molecular Pathology; Royal College of Pathologists. Guidance for laboratories performing molecular pathology for cancer patients. J Clin Pathol. 2014;67(11):923–31.
  6. Michielin O, et al; ESMO Guidelines Committee. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019 Sept 30 [Epub ahead of print]. https://www.esmo.org/Guidelines/Melanoma/Cutaneous-Melanoma. Accessed October 16, 2019.