Innovations in Oncology Learning Center: From Guidelines to Practice: Melanoma

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Dr. Tawbi: 
This is CME on ReachMD, and I'm Dr. Hussein Tawbi. Here with me today is Dr. Sapna Patel. Welcome, Dr. Patel, and let's review a case of a patient with newly diagnosed BRAF-mutant metastatic melanoma stage IV. 

So this is a 65-year-old gentleman who was diagnosed a few years ago, exactly about 3 years ago, with a deep primary melanoma of the right forearm that was 4.8 mm, ulcerated, but had no sentinel lymph nodes, and was actually followed on consistent scans every 3 to 6 months, did not receive any adjuvant therapy. And most recently, on a PET/CT that was done a month ago, was found to have multiple lymph nodes and lung metastases. Biopsy proven to be metastatic melanoma. He is known to be BRAF mutated. His LDH is normal. I will tell you. He has all of the typical comorbidities of a patient that age, hyperlipidemia, GERD, and is a former smoker as well. 

So, Dr. Patel, how would you approach a patient like this with metastatic melanoma that is BRAF mutated and newly diagnosed?

Dr. Patel: 
Yeah, this is a great case, Hussein. It's a T4b originally. Of course, you're describing it a case of potentially N2 or N3 disease, if these are regional lymph nodes, and then M1b disease with the lung involvement. And this is a case of a patient with a BRAF mutation, so obviously we have a few options where we could sequence immunotherapy, start out with immunotherapy first, and reserve BRAF/MEK inhibitor therapy. We could consider starting with immunotherapy and having a planned switch to BRAF/MEK inhibitor. Or we could say we need to start with BRAF/MEK inhibitor up front. 

So let's start with the first option of starting with immunotherapy. This comes from the EA6134 DREAMseq trial. We know that the majority of patients that harbor a BRAF mutation still do better starting with combination checkpoint immunotherapy. In the case of the DREAMseq trial, it was nivolumab/ipilimumab. But one probably believes you could infer the same with nivolumab/relatlimab. And starting with that and then switching to BRAF/MEK-targeted therapy only at progression or if needed. 

There's another trial that's quite intriguing, called SECOMBIT trial, sequential combination immunotherapy targeted therapy trial, where you didn't wait for disease progression; you actually did a planned switch at about 8 weeks of therapy. And in that case, it was a switch to BRAF/MEK-targeted therapy. 

So one option would be start with combination immunotherapy, change at progression. The other option would be starting with targeted therapy and a planned switch after 8 weeks or 12 weeks to immunotherapy. But we actually think starting with combination targeted therapy really only needs to be reserved for a certain patient population. 

So in general, even in the face of a BRAF mutation, we like frontline combination immunotherapy for metastatic melanoma.

Dr. Tawbi: 
Yeah, thank you, Sapna. I mean, that was exactly kind of the presentation of a case that was not really symptomatic but had significant tumor burden. And it's really not just about the tumor burden as much as about how much symptoms and how much runway do you have. 

I was interested in your specific kind of mention of you could do ipi/nivo, you could do nivo/rela in this situation. What is your perspective on that? Because I think we just favor immunotherapy period, and then you have basically the choice between the 2.

Dr. Patel: 
Yeah. So we have frontline data now for nivo/ipi. We have frontline data for nivo/relatlimab. There's some indirect treatment comparisons that suggest these treatments are really kind of equal in terms of efficacy, and we know that nivolumab/relatlimab carries a lesser toxicity rate. So I think it's in the comfort of the practitioner. 

I think one small nuance in here is from the patient perspective. Nivolumab/ipilimumab tends to have a longer treatment-free interval, mainly because patients run into toxicity, and that's what causes them to go off treatment, whereas nivolumab/relatlimab is more of a steady course of treatment for patients. Would a patient want kind of some therapy that might cause a toxicity, but give them a treatment-free interval, versus something kind of more steady and less risky for side effects?

Dr. Tawbi: 
Great points. Well, thank you so much. I think our time is up. Thank you, Dr. Patel.