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Locoregional Therapy for Advanced Melanoma

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 Online: Wednesday, Nov 08, 2017



Transcript: 

Jeffrey S. Weber, MD, PhD: In the remaining time, let’s talk about something close to my heart, which is the management of locoregional therapy. Let me turn to Michael. None of us are surgeons, but I think we all have to discuss with patients the potential management of resectable disease. How do you talk to patients about whether or not you could have a surgeon resect their tumor, and how do you decide what’s resectable and what’s not?

Michael A. Postow, MD: It’s a really common question when someone gets a diagnosis of melanoma: stage 3 melanoma, for example, involving a lymph node, or in some situations what’s called oligometastatic stage 4, with maybe 1 lung lesion or 1 area on the skin and a lymph node. A lot of patients ask, “Well, what about just removing the tumor? Can you just operate and get this tumor out of me? I don’t want it in me anymore.” Yes, you could talk about all the drugs that we’re discussing here today, but they say, “I don’t want to go on any of these. I don’t want infusions. I don’t want pills. I just want surgery to remove all this.” So, how do we think about that now in the current era?

I think the complications of the conversation are getting more and more complex, because we have now some very effective systemic treatment. And the real question is, what is the role of surgery in some of these situations? The standard of care for patients who present with stage 3 melanoma—especially those who clinically present with stage 3 melanoma, like a lymph node in an armpit, for example—is to surgically remove it and then consider that patient for adjuvant treatment. So, while we are talking about some different clinical approaches that we may want to handle for that patient, I think we should keep in mind the standard approach for stage 3 resectable melanoma is surgery and then consideration for adjuvant treatments.

However, we are seeing a change in some neoadjuvant clinical trials that are emerging at this moment. We are treating some of these patients with resectable stage 3 melanoma with neoadjuvant approaches, either BRAF and MEK inhibitors as a neoadjuvant strategy, single agent PD-1, or combinations of ipilimumab and PD-1 prior to surgical resection. These are intended to try to make the surgery an easier surgery, to shrink the tumor and make it more resectable. They’re also intended to treat the micrometastatic disease, which invariably would, unfortunately, lead to recurrence down the line if we were only to pursue surgery alone.

We have a lot of questions about what the role of neoadjuvant systemic treatment will ultimately be in locoregional management. We have a lot of ongoing questions about what the role of adjuvant treatments will be after surgical resection. We’re hearing at ESMO this year about a lot of new updates in all of these areas, and it’s going to be an ongoing, complicated conversation.

Jeffrey S. Weber, MD, PhD: I guess there are a couple of neoadjuvant abstracts. One was by Alex Menzies from Australia, and there was another one where they talked about ipilimumab/nivolumab adjuvant therapy. They had both ipilimumab/nivolumab and dabrafenib/trametinib.

Reinhard G. Dummer, MD: That’s from Amsterdam, the Netherlands.

Jeffrey S. Weber, MD, PhD: They’re from Amsterdam, the Netherlands. Caroline, this is all really recent, but what did they see?

Caroline Robert, MD, PhD: It’s very encouraging in the sense that very often, you have a complete response that is seen pathologically. The real question is, what is going to become of following the patients? Because we don’t know how long to treat, after all. So, these patients have big, palpable stage 3 disease, but in fact, the reality is that we think they might have stage 4 disease. So, we’re in a situation with a very small burden of stage 4 disease. How long to treat, this is the real question. But it’s interesting, and of course, we have to encourage this kind of trial, which will give us a lot of information concerning the translational research.

I would like to make this point at this moment, because as we all say, we have to work in very close collaboration with our surgeons, our radiotherapists. For example, we have a good team of interventionist radiologists who help us to do the biopsy when it’s not so easy or the injection of the drug when it is not so easy for us. Meaning that, with all of the new drugs that we have, not only our job is changing and our paradigm is changing, but also all of the colleagues who are surrounding us and our patients are changing. In my hospital, I never had a surgeon telling me, as it could happen, before, “I’m not going to do surgery for your patient. It’s a metastatic melanoma. I’m not going to use my time to do that or to do several sessions of radiotherapy.” They change the whole face of medicine, these new drugs.

Jeffrey S. Weber, MD, PhD: I would agree.

Transcript Edited for Clarity 

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Transcript: 

Jeffrey S. Weber, MD, PhD: In the remaining time, let’s talk about something close to my heart, which is the management of locoregional therapy. Let me turn to Michael. None of us are surgeons, but I think we all have to discuss with patients the potential management of resectable disease. How do you talk to patients about whether or not you could have a surgeon resect their tumor, and how do you decide what’s resectable and what’s not?

Michael A. Postow, MD: It’s a really common question when someone gets a diagnosis of melanoma: stage 3 melanoma, for example, involving a lymph node, or in some situations what’s called oligometastatic stage 4, with maybe 1 lung lesion or 1 area on the skin and a lymph node. A lot of patients ask, “Well, what about just removing the tumor? Can you just operate and get this tumor out of me? I don’t want it in me anymore.” Yes, you could talk about all the drugs that we’re discussing here today, but they say, “I don’t want to go on any of these. I don’t want infusions. I don’t want pills. I just want surgery to remove all this.” So, how do we think about that now in the current era?

I think the complications of the conversation are getting more and more complex, because we have now some very effective systemic treatment. And the real question is, what is the role of surgery in some of these situations? The standard of care for patients who present with stage 3 melanoma—especially those who clinically present with stage 3 melanoma, like a lymph node in an armpit, for example—is to surgically remove it and then consider that patient for adjuvant treatment. So, while we are talking about some different clinical approaches that we may want to handle for that patient, I think we should keep in mind the standard approach for stage 3 resectable melanoma is surgery and then consideration for adjuvant treatments.

However, we are seeing a change in some neoadjuvant clinical trials that are emerging at this moment. We are treating some of these patients with resectable stage 3 melanoma with neoadjuvant approaches, either BRAF and MEK inhibitors as a neoadjuvant strategy, single agent PD-1, or combinations of ipilimumab and PD-1 prior to surgical resection. These are intended to try to make the surgery an easier surgery, to shrink the tumor and make it more resectable. They’re also intended to treat the micrometastatic disease, which invariably would, unfortunately, lead to recurrence down the line if we were only to pursue surgery alone.

We have a lot of questions about what the role of neoadjuvant systemic treatment will ultimately be in locoregional management. We have a lot of ongoing questions about what the role of adjuvant treatments will be after surgical resection. We’re hearing at ESMO this year about a lot of new updates in all of these areas, and it’s going to be an ongoing, complicated conversation.

Jeffrey S. Weber, MD, PhD: I guess there are a couple of neoadjuvant abstracts. One was by Alex Menzies from Australia, and there was another one where they talked about ipilimumab/nivolumab adjuvant therapy. They had both ipilimumab/nivolumab and dabrafenib/trametinib.

Reinhard G. Dummer, MD: That’s from Amsterdam, the Netherlands.

Jeffrey S. Weber, MD, PhD: They’re from Amsterdam, the Netherlands. Caroline, this is all really recent, but what did they see?

Caroline Robert, MD, PhD: It’s very encouraging in the sense that very often, you have a complete response that is seen pathologically. The real question is, what is going to become of following the patients? Because we don’t know how long to treat, after all. So, these patients have big, palpable stage 3 disease, but in fact, the reality is that we think they might have stage 4 disease. So, we’re in a situation with a very small burden of stage 4 disease. How long to treat, this is the real question. But it’s interesting, and of course, we have to encourage this kind of trial, which will give us a lot of information concerning the translational research.

I would like to make this point at this moment, because as we all say, we have to work in very close collaboration with our surgeons, our radiotherapists. For example, we have a good team of interventionist radiologists who help us to do the biopsy when it’s not so easy or the injection of the drug when it is not so easy for us. Meaning that, with all of the new drugs that we have, not only our job is changing and our paradigm is changing, but also all of the colleagues who are surrounding us and our patients are changing. In my hospital, I never had a surgeon telling me, as it could happen, before, “I’m not going to do surgery for your patient. It’s a metastatic melanoma. I’m not going to use my time to do that or to do several sessions of radiotherapy.” They change the whole face of medicine, these new drugs.

Jeffrey S. Weber, MD, PhD: I would agree.

Transcript Edited for Clarity 
View Conference Coverage
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