Jeffrey Weber, MD, PhD: Factors to Consider When Determining Treatment

What factors do you consider when determining treatment for patients like Charles?

When patients initially present with a diagnosis of metastatic melanoma, I try to group them into categories. I try to group them by indolent disease, low disease burden, three or fewer sites of disease, and normal LDH. That’s one category which luckily is seen perhaps in the majority of patients. Then I look to the high LDH, the abnormal LDH, the high tumor burden. We’re talking about multiple centimeters worth of linear tumor, abnormal performance status, and symptomatic, which goes with the performance status of 1 or even 2. So, in one category is the good actors, in the other category is the bad actors.

When you think about a patient who’s BRAF mutated, obviously you need to decide if they are V600 mutated or not. But, of course, when you have a V600 mutated patient, you have to decide if you’re going to start treatment with BRAF/MEK first; that’s generally going to be in the category of patients where you need a quick response. Paradoxically, based on data that we’ve seen recently published, it’s the opposite category that also would be attractive for the use of BRAF/MEK inhibition. That’s the normal LDH, low disease burden, very indolent disease.

This particular patient falls into a middle category. Charles is a patient who already has an abnormal performance status of 1. He has symptoms. In fact, he presented with eight weeks of symptoms, so the disease in Charles’s lungs is actually causing issues for him. On the other hand, he does have a normal LDH and he probably has multiple metastases, so he probably has more than three sites of disease. This is someone where you might want to get in a quick hit with BRAF/MEK and then you might want to consider reverting to the use of immunotherapy. One creative approach that I take is if someone is in the middle range or has a high disease burden and/or is symptomatic, I might give them four to eight weeks of BRAF plus MEK and then do essentially what we would call a forced switch to IPI plus NIVO if I thought they had enough disease burden. And, if not, I might go with just a PD-1 drug alone.

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.