Jeffrey S. Weber, MD, PhD: Hello, and thank you for joining this OncLive® Peer Exchange® titled “New Treatment Paradigms for Advanced Melanoma.” During the past several years, the availability of immuno-oncology agents and mutation-targeted therapies has transformed the way we treat advanced melanoma. As medical oncologists, we are bombarded by new and exciting data, often providing multiple choices for treating the patient that’s sitting in front of us. In this OncLive® Peer Exchange® discussion, I’m joined by leaders in the field of melanoma clinical research. Our goal is to provide you with clinical context surrounding the data to better inform your treatment decisions. In today’s discussion, we’ll explore some of the important research coming out of the 2018 ASCO Annual Meeting. We’ll focus on the latest information surrounding the use of adjuvant therapy and will discuss new options for the treatment of metastatic disease.
I’m Dr. Jeffrey Weber, deputy director of the Laura and Isaac Perlmutter Cancer Center and professor of medicine at NYU Langone Medical Center in New York City. Participating today on our distinguished panel are Dr. Robert Andtbacka, a professor in the Department of Surgery at the University of Utah School of Medicine and investigator at the Huntsman Cancer Institute in Salt Lake City, Utah; Dr. Omid Hamid, chief of research and immuno-oncology at The Angeles Clinic and Research Institute and codirector of the Cutaneous Malignancy Program at Cedars-Sinai Medical Center in Los Angeles, California; Dr. Jason Luke, an assistant professor of medicine and medical oncologist at the University of Chicago in Chicago, Illinois; Dr. Michael Postow, an assistant attending physician in the Melanoma and Immunotherapeutics Oncology Service at Memorial Sloan Kettering Cancer Center in New York City; and Dr Hussein Tawbi, associate professor and director of Clinical Research and Early Drug Development in the Department of Melanoma Medical Oncology and a member of the Department of Investigational Cancer Therapeutics at The UT MD Anderson Cancer Center in Houston, Texas. Thank you all for joining us. Let’s begin.
There has been an awful lot of action and a lot of research and development in the adjuvant field in melanoma within the last year, with 3 very impressive trials and multiple new approvals. This brings up a host of issues. One of the first issues we think about is, who gets operated on and who doesn’t? Then, who gets adjuvant therapy? Robert, how do you decide? What are the criteria for resecting a patient who has either stage 3 or stage 4 melanoma? Who’s resectable and who’s not?
Robert Andtbacka, MD, CM: That’s a very good question, Jeff, and it is something we deal with every day in our practice with patients. In the stage 3 setting, we really have to divide patients into the ones who have microscopic disease in their lymph nodes versus the patients who present with bulky disease and macroscopic disease. First, if we look at the patients with microscopic disease, a year ago we would have recommended that pretty much all patients—if they had microscopic disease in a lymph node basin—get a completion lymph node dissection.
There are 2 important studies that have presented results asking the question of, do we really need to do that? In those studies, patients were randomized to either have a completion lymph node dissection, which would have been the standard of care, or ultrasound follow-up, if they had disease in the lymph node basin. Both of these studies looked at the survival in these patients, and there were slightly different types of survivals. The MSLT-II study, which was the larger study, looked at melanoma-specific survival. There really was no difference in the patients who had a partial sentinel lymph node dissection, who underwent the completion lymph node dissection, versus an ultrasound follow-up in melanoma-specific survival in that patient population.
We have to remember that the only patients who really benefit from surgery—from additional surgery, if they have a positive sentinel lymph node—are the patients with additional disease in their lymph node basin. They account for about 25% of all patients. That means that 75% of patients will not have benefited from this operation at all. The second study was a German study. This was a slightly smaller study, also looking at distant metastasis-free survival for these patients. The study looked at a similar patient population. Again, there was no difference in survival for those patients. One of the caveats with both of these studies was that the amount of tumor in the sentinel lymph node was fairly small. When we think about these patients, we have to remember that most patients just had 1 positive sentinel lymph node. When we did a completion lymph node dissection, we did not necessarily find additional lymph nodes with melanoma in them. The tumor burden in those sentinel lymph nodes was also quite small.
In my practice, in these patients, following these patients with an ultrasound is a very viable option. I would say that more than half of the patients wish to just follow up with an ultrasound.
Jeffrey S. Weber, MD, PhD: How often do you do it?
Robert Andtbacka, MD, CM: In my practice, we probably do it about 20%, 30% of the time, when we do a completion lymph node dissection. This tends to be for patients who presented with a large amount of disease in the lymph node basin and also for patients with multiple lymph nodes with melanoma in them. I still think that remains…controversial. We know that in these patients, after we’ve done the completion lymph node dissection, they are at high risk of local recurrence but also for distant recurrence. These are patients who we would always discuss adjuvant treatment with. In the adjuvant studies that have been done, all patients who went on the adjuvant studies had to have a completion lymph node dissection. I think one of the controversies is that we don’t fully know what the benefit of the adjuvant therapy is, if the patient has not had a completion lymph node dissection. Having said that, I still think that the minority of our patients now get a completion lymph node dissection.
Jeffrey S. Weber, MD, PhD: And interestingly, I don’t think there’s ever going to be an adjuvant study in patients in that category, given that we have multiple positive studies, which we’ll talk about in a few minutes. I don’t think that’s ever going to happen. So, as often happens in medicine, we use the best data that we have available, and we’ll be extrapolating.
Transcript Edited for Clarity