Hussein Tawbi, MD, PhD reviews a case study of a 47-year-old woman with BRAF-mutated metastatic melanoma and discusses his approach to workup, including biomarker testing, for patients with the disease.
Hussein Tawbi, MD, PhD: Hello. My name is Hussein Tawbi. I'm a melanoma medical oncologist at MD Anderson Cancer Center. I'm professor and deputy chair of the Department of Melanoma Medical Oncology and co-director of the Brain Metastasis Clinic here at MD Anderson Cancer Center. What we're discussing today is a case of an unfortunate lady in her 40s, specifically a 47-year-old lady who presented with a 2.2-millimeter primary melanoma of the skin of her left thigh. On history, she did report the history of prior tanning bed use. She was an excellent performance status. After a wide local excision and a sentinel lymph node biopsy, she was found to have two positive inguinal lymph nodes. At least one of them had a two-millimeter deposit. Then proceeded to have a systemic staging with a CT of the chest, abdomen, and pelvis that did reveal one lesion in the right lower lobe of her lung. She has one metastatic lesion to the lung that measured 1.8 centimeters. We did proceed with a biopsy that did confirm this to be metastatic melanoma. As part of her staging, as we do for all of our patients with metastatic melanoma, we do image the brain. In fact, her brain MRI was negative. We did test her serum LDH level, which showed an elevated LDH at 456 international units. We did also perform NextGen test sequencing, and she was found to have a B-RAF V600E mutation. The patient is presenting to discuss for treatment options with us.
The typical patients that we see presenting with de novo metastatic melanoma fits into I would say a couple of categories. I wouldn't say that there's one type that is the patients that present to us. We do have as you may know, generally metastatic melanoma and melanoma is a disease actually of the elderly. Typically we find patients that are in their 60's who are presenting with their first diagnosis of metastatic melanoma. The segment of the population that's seeing the highest incidence increase is actually older white males. This is kind of a typical situation. We also experience unfortunately because of melanoma being a disease that can affect younger individuals especially after prior significant sun exposure, like tanning bed or kind of just generally a lot of prior childhood sunburns as well. We also see a younger patient population occasionally show up. This particular patient, that 47-year-old, I would say to your question is very consistent with the typical patient population that we see.
Hussein Tawbi, MD, PhD: For all patients that present with melanoma, I would say stage three and above we really highly recommend performing mutational testing, at least for the B-RAF mutation. Then ideally NextGen sequencing that not only identifies the B-RAF mutation but can identify a couple of other potentially targetable genes. Within the standard of care, we only have B-RAF and MEK inhibitors that are available for patients that have B-RAF activating mutations. But we also have actually an FDA approval for a very small segment of melanoma patients. Namely patients with NTRK fusions. There are two drugs, Entrectinib and Larotrectinib that are FDA approved for that population. That requires also you know a specific an NextGen sequencing. I do recommend doing that. However, across the board, the B-RAF mutation is the most consistent and relevant mutation that I recommend for all patients with at least stage three melanoma. In terms of other biomarkers that do matter, melanoma PD-L1 testing is not very relevant or important. It is not something that I obtain on my patients. If a patient comes in that has already been tested for PD-L1 status I consider it a variable of interest, but I almost never base my decision solely on a PD-L1 expression. We also care in melanoma, especially in the metastatic disease setting about LDH level. As you heard about this lady, we did check LDH because it is a prognostic marker. I wish we had predictive markers, but LDH is not very predictive as much as it is prognostic. The patients that have a higher LDH levels typically have worse outcomes overall. We know that for those patients, we may want to consider being generally kind of more aggressive.
Hussein Tawbi, MD, PhD: That's a great question. In the adjuvant setting, I do. Today's discussion is not focused on that population. Just to be sure in the stage three setting, we have to make sure that patients are aware of all of the options that are available to them. As you'll hear later in our discussion today, until a couple of years ago we used to really struggle between whether we should treat our patients with targeted therapies upfront or systemic therapies upfront or immunotherapies to be specific. I have to say that with recent results from DREAMseq that we were going to discuss soon, that has become less relevant. We generally start our patients on immunotherapy, and therefore we don't have to wait for the result of the B-RAF mutation. But ideally, we would have it in hand as soon as possible.