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Metastatic Melanoma: The Immunotherapy Approach

Panelists: Jeffrey S. Weber, MD, PhD, NYU Langone Health; Reinhard G. Dummer, MD, University Hospital of Zurich; Axel Hauschild, MD, PhD, University Hospital Schleswig-Holstein; Michael A. Postow, MD, Memorial Sloan Kettering Cancer Center; Caroline Robert, MD, PhD, Gustave-Roussy
Published: Tuesday, Oct 03, 2017



Transcript: 

Jeffrey S. Weber, MD, PhD: Hello, and thank you for joining this OncLive® Peer Exchange® entitled, “Advances in Systemic Therapy for Melanoma.” We’ve made enormous strides in developing novel therapies for advanced melanoma over the last 6 years, particularly in the field of immuno-oncology where melanoma has been at the forefront of paradigm-defining progress. We continue to see new advances at an accelerated pace, as we learn more about the disease itself and how to treat it. Today, I am joined by a panel of international experts in the field of melanoma research. Together we will discuss the studies presented at ESMO 2017 and will provide you with perspective on how those data relate to clinical practice.

I am Dr. Jeffrey Weber. I’m a professor in the Department of Medicine and deputy director of the Laura and Isaac Perlmutter Cancer Center, as well as co-director of the Melanoma Research Program at NYU Langone Health in New York City.

Participating today on our distinguished panel are Dr. Reinhard Dummer, professor at the University of Zürich and vice chairman of the Department of Dermatology at the University Hospital of Zürich, Switzerland; Dr. Axel Hauschild, professor and head of the Department of Dermatology in the Interdisciplinary Skin Cancer Center at the University Hospital Schleswig-Holstein in Kiel, Germany; Dr. Michael Postow, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City; and Dr. Caroline Robert, chairman of the Dermatology Committee at Institute Gustave Roussy in Paris, France.

Thank you so much for joining us. Let’s begin. First, Caroline, tell me about your personal approach to using immunotherapy in patients with metastatic disease. How do you make decisions as to what to use and how to use it?

Caroline Robert, MD, PhD: It is true that for the last few years we have totally changed our way of treating patients. If you imagine somebody having stopped working in the field and coming back now, they would not be able to use any of the drugs that we use today. Immunotherapy is a revolution, and I must say that if I have a patient with a disease that is not growing too rapidly and is not immediately threatening, I would choose immunotherapy as a first choice. If your question concerns which immunotherapy to use, I would say, it depends. Because right now, combinations of immunotherapy with ipilimumab plus nivolumab or anti–PD-1 only—we have 2 possibilities, pembrolizumab or nivolumab—depend on the country. In France, presently, we don’t have the reimbursement for combination, but it is going to happen very soon.

Jeffrey S. Weber, MD, PhD: And do you routinely using PD-L1 staining to make decisions as to who to treat or how to treat them?

Caroline Robert, MD, PhD: I do PD-L1 staining, but I do it from a research perspective. I don’t rely on that for one particular patient. We know that the predictive positive and negative values are not very good at the individual level. This is not a good enough biomarker, but it is interesting, and we work on that in the lab to try to identify other markers that are more predictive.

Jeffrey S. Weber, MD, PhD: We do have a couple of choices, at least with respect to the PD-1 antibodies approved in most countries in the EU, Canada, Australia, and the US for melanoma. Do you think there’s any difference or are there any data to support there being a difference between pembrolizumab and nivolumab?

Caroline Robert, MD, PhD: I don’t think so. I think they have the same efficacy and the same safety profile. The regimen is different. One is given every 2 weeks, one is given every 3 weeks. I’m not actually sure if this has a rationale to inject every 2 or every 3 weeks, but this is how we prescribe the drug. I presented at the present ESMO meeting the long-term results of patients, especially the good patients—the patients who had a complete response. We have data from pembrolizumab, we have data from nivolumab, and we have data from the combination of nivolumab and ipilimumab. What we can say from these data is that if you have a complete response, most of the time now we have long follow-up. It’s durable. The vast majority of these patients responding completely are still in complete response after a median follow-up of close to 4 years. So, this is very good news.

Jeffrey S. Weber, MD, PhD: What about the stable patients though? You get a lot of patients who have a suboptimal response or maybe a stable disease. If you treat someone with pembrolizumab or nivolumab up front and you get just stability, what’s your next move? Reinhard?

Reinhard G. Dummer, MD: Well, if they have stable disease, I actually continue the treatment. A number of patients see a delayed response. Actually, some patients who don’t really show shrinkage, especially if we start with a low tumor burden. So, this does not really make me nervous. Even in situations where I have, let’s say, an elderly patient who has an oligometastatic disease and only 1 lesion is starting to grow, we have resected some of these lesions. We do stereotactic irradiations if the disease is controlled. So, a number of patients are still on treatment despite what I would call minor progress. There are data on treatment beyond progression that really support this strategy.

Jeffrey S. Weber, MD, PhD: That’s part of the Rip Van Winkle effect. You were thinking of Rip Van Winkle, the man who went to sleep for a huge amount of time and then woke up and the world was completely changed.

Caroline Robert, MD, PhD: Ah, yes.

Jeffrey S. Weber, MD, PhD: That sounds like something we would never have done. Would you agree?

Caroline Robert, MD, PhD: Exactly.

Axel Hauschild, MD, PhD: Yes, I will agree, but I think we have data from ASCO that are indicating even patients with stable disease have long-term benefit. I was surprised to see the first analysis of CRs: the duration of CRs; the duration of PRs, which is very much reflecting the situation of CRs; and for the very first time, the duration of stabilized diseases. Obviously, if you give immunotherapy, this matters. It means the patient has some sort of benefit. Even if you stop the treatment for various reasons—it could be toxicity or the willingness of patients to be treated—you still have a good response, which is maintained. Therefore, I wouldn’t change therapy unless the patient is aiming for a complete response, and we all know that complete responders are the patients with whom we discuss, carefully, a cure in our days.

Transcript Edited for Clarity 

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Transcript: 

Jeffrey S. Weber, MD, PhD: Hello, and thank you for joining this OncLive® Peer Exchange® entitled, “Advances in Systemic Therapy for Melanoma.” We’ve made enormous strides in developing novel therapies for advanced melanoma over the last 6 years, particularly in the field of immuno-oncology where melanoma has been at the forefront of paradigm-defining progress. We continue to see new advances at an accelerated pace, as we learn more about the disease itself and how to treat it. Today, I am joined by a panel of international experts in the field of melanoma research. Together we will discuss the studies presented at ESMO 2017 and will provide you with perspective on how those data relate to clinical practice.

I am Dr. Jeffrey Weber. I’m a professor in the Department of Medicine and deputy director of the Laura and Isaac Perlmutter Cancer Center, as well as co-director of the Melanoma Research Program at NYU Langone Health in New York City.

Participating today on our distinguished panel are Dr. Reinhard Dummer, professor at the University of Zürich and vice chairman of the Department of Dermatology at the University Hospital of Zürich, Switzerland; Dr. Axel Hauschild, professor and head of the Department of Dermatology in the Interdisciplinary Skin Cancer Center at the University Hospital Schleswig-Holstein in Kiel, Germany; Dr. Michael Postow, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City; and Dr. Caroline Robert, chairman of the Dermatology Committee at Institute Gustave Roussy in Paris, France.

Thank you so much for joining us. Let’s begin. First, Caroline, tell me about your personal approach to using immunotherapy in patients with metastatic disease. How do you make decisions as to what to use and how to use it?

Caroline Robert, MD, PhD: It is true that for the last few years we have totally changed our way of treating patients. If you imagine somebody having stopped working in the field and coming back now, they would not be able to use any of the drugs that we use today. Immunotherapy is a revolution, and I must say that if I have a patient with a disease that is not growing too rapidly and is not immediately threatening, I would choose immunotherapy as a first choice. If your question concerns which immunotherapy to use, I would say, it depends. Because right now, combinations of immunotherapy with ipilimumab plus nivolumab or anti–PD-1 only—we have 2 possibilities, pembrolizumab or nivolumab—depend on the country. In France, presently, we don’t have the reimbursement for combination, but it is going to happen very soon.

Jeffrey S. Weber, MD, PhD: And do you routinely using PD-L1 staining to make decisions as to who to treat or how to treat them?

Caroline Robert, MD, PhD: I do PD-L1 staining, but I do it from a research perspective. I don’t rely on that for one particular patient. We know that the predictive positive and negative values are not very good at the individual level. This is not a good enough biomarker, but it is interesting, and we work on that in the lab to try to identify other markers that are more predictive.

Jeffrey S. Weber, MD, PhD: We do have a couple of choices, at least with respect to the PD-1 antibodies approved in most countries in the EU, Canada, Australia, and the US for melanoma. Do you think there’s any difference or are there any data to support there being a difference between pembrolizumab and nivolumab?

Caroline Robert, MD, PhD: I don’t think so. I think they have the same efficacy and the same safety profile. The regimen is different. One is given every 2 weeks, one is given every 3 weeks. I’m not actually sure if this has a rationale to inject every 2 or every 3 weeks, but this is how we prescribe the drug. I presented at the present ESMO meeting the long-term results of patients, especially the good patients—the patients who had a complete response. We have data from pembrolizumab, we have data from nivolumab, and we have data from the combination of nivolumab and ipilimumab. What we can say from these data is that if you have a complete response, most of the time now we have long follow-up. It’s durable. The vast majority of these patients responding completely are still in complete response after a median follow-up of close to 4 years. So, this is very good news.

Jeffrey S. Weber, MD, PhD: What about the stable patients though? You get a lot of patients who have a suboptimal response or maybe a stable disease. If you treat someone with pembrolizumab or nivolumab up front and you get just stability, what’s your next move? Reinhard?

Reinhard G. Dummer, MD: Well, if they have stable disease, I actually continue the treatment. A number of patients see a delayed response. Actually, some patients who don’t really show shrinkage, especially if we start with a low tumor burden. So, this does not really make me nervous. Even in situations where I have, let’s say, an elderly patient who has an oligometastatic disease and only 1 lesion is starting to grow, we have resected some of these lesions. We do stereotactic irradiations if the disease is controlled. So, a number of patients are still on treatment despite what I would call minor progress. There are data on treatment beyond progression that really support this strategy.

Jeffrey S. Weber, MD, PhD: That’s part of the Rip Van Winkle effect. You were thinking of Rip Van Winkle, the man who went to sleep for a huge amount of time and then woke up and the world was completely changed.

Caroline Robert, MD, PhD: Ah, yes.

Jeffrey S. Weber, MD, PhD: That sounds like something we would never have done. Would you agree?

Caroline Robert, MD, PhD: Exactly.

Axel Hauschild, MD, PhD: Yes, I will agree, but I think we have data from ASCO that are indicating even patients with stable disease have long-term benefit. I was surprised to see the first analysis of CRs: the duration of CRs; the duration of PRs, which is very much reflecting the situation of CRs; and for the very first time, the duration of stabilized diseases. Obviously, if you give immunotherapy, this matters. It means the patient has some sort of benefit. Even if you stop the treatment for various reasons—it could be toxicity or the willingness of patients to be treated—you still have a good response, which is maintained. Therefore, I wouldn’t change therapy unless the patient is aiming for a complete response, and we all know that complete responders are the patients with whom we discuss, carefully, a cure in our days.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Evolving Roles for Targeted Melanoma Therapies: Assessing Rapid Progress in the Field and Looking Toward Future CombinationsFeb 28, 20191.5
Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
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