Metastatic Melanoma with Adil Daud, MD and Boris C. Bastian, MD, PhD - Episode 5

Adil Daud, MD: Frequency of Missed BRAF Alterations in Melanoma

How frequently are BRAF alterations missed that are subsequently picked up using a different test, and should a second test always be used if results are negative?

Just to take a step back, I think about 50% of patients with melanoma will have BRAF-mutant disease and 50% have BRAF-negative disease. I think if you look back at the performance of different types of tests, what’s interesting is that a lot of tests are very sensitive for V600E mutations but not so much for V600K and D and some of the less frequent V600 mutations. In our center we use immunohistochemistry testing, which is more sensitive for V600E but not for the other lesser frequent V600 type mutations in BRAF. So for the patients who are BRAF-negative by the first screening test that’s used, it’s common practice at our center to retest them using a more high fidelity test, either using next-generation sequencing, that’s what we do, or you could use the bioMérieux test or some of the other tests that employs Sanger sequencing.

I think what’s interesting in the whole BRAF testing field is that the FDA approved test is not actually specific for V600E mutations. It will just pick up any changes in the V600 position. So it can pick up some other V600 mutations but not necessarily pick up all of the V600Es, and some of the other tests have their own peculiarities. So it’s a good idea to test people who were negative with the first-generation or the first screening test because a lot of those are more specific than they are sensitive.

CASE: Metastatic Melanoma

Michelle is a 55-year old who was referred by her primary care physician to receive a biopsy for a suspicious mole during a routine visit. Results of the biopsy and other subsequent tests revealed that she had an M1b stage tumor (lung metastasis and a less than ULN LDH level). Her ECOG PS is 0.

  • Initial BRAF testing using a laboratory-developed test was negative for BRAF V600E L

She was referred from the community setting to a tertiary center, at which point a second test was conducted using the bioMérieux HxID-BRAF kit. This assay was positive for the BRAF V600K mutation

  • Following the finding ofBRAF-positivity, Michelle was prescribed the combination of dabrafenib (150 mg BID) and trametinib (1 mg daily)