Jeffrey Weber, MD, PhD: The Impact of BRAF/MEK Inhibitors in Melanoma

What impact have BRAF/MEK inhibitors had, since their initial approval, and how has this changed mutation testing for melanoma?

The approval of the first BRAF inhibitor, vemurafenib then followed by dabrafenib, and then the combo with dabrafenib/trametinib has essentially dictated that virtually every patient with stage III or above melanoma, that is all the stage IIIs and all the metastatic stage IVs, are getting genomic testing. It started out just with the Cobas test, then it was pyrosequencing, and then it was multiple gene panels, then it was large multi-gene panels. Over a span of about three or four years at Moffitt where I formerly worked, we went from a single gene to five genes to 30 genes, 50 genes, and very soon at my institution at NYU we’ll have a 500-gene panel. It means that there’s been an explosion of genetic testing in patients with melanoma.

The irony is relatively few of them are actionable. In fact, in the standard of care melanoma business in the community, really only one of them is actionable and that’s BRAF. For pretty much the same price, you get dozens of genes, which up the road will provide valuable information because if those patients progress at a time when other targeted drugs are more easily accessible to patients, there will be benefit for the patients to know that information.

CASE: Metastatic Melanoma

Charles, a 62-year-old Caucasian landscaper, presented to his primary care physician with fatigue, dyspnea upon exertion, and a nonproductive cough that has lasted for 6 to 8 weeks. .

• Following a medical examination, a suspicious mole was biopsied, which resulted in a diagnosis of melanoma.
• Genetic testing revealed aBRAFV600K mutation
• PET/CT scan shows metastases to the lung and a soft tissue nodule in the liver (1.4 cm x 1.1 cm)
• LDH levels and liver function test results were normal
• The patient’s ECOG performance status was 1

Treatment was initiated with the combination of BRAF and MEK inhibitors.