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Sequencing Strategies for Recurrent/Refractory Melanoma

Panelists: Jeffrey Weber, MD, PhD, NYU Langone Medical Center; Reinhard Dummer, MD, University of Zurich Hospital;Axel Hauschild, MD, University of Kiel;Caroline Robert, MD, PhD, Gustave Roussy; Dirk Schadendorf, MD, University Hospital Essen
Published: Wednesday, Jan 11, 2017


Transcript:

Jeffrey Weber, MD, PhD:
Have you ever given someone targeted therapy, they progressed, gone on to immunotherapy, and gone back to targeted therapy?

Caroline Robert, MD, PhD: Sure.

Reinhard Dummer, MD: Oh, yes.

Dirk Schadendorf, MD: Yes.

Axel Hauschild, MD: Yes.

Jeffrey Weber, MD, PhD: Caroline, have you done it successfully? Let me rephrase the question now.

Caroline Robert, MD, PhD: Well, I don’t have exact numbers, but we’ve done that routinely, actually. You treat, their resistance develops, you give immunotherapy, and then what do you do? You go back to targeted therapy and very often, you have a response. But it doesn’t mean that this response would last for a very long time. It depends.

Axel Hauschild, MD: My impression is that if you really expose them, or let’s say rechallenge them, they still have good response, but the response duration is much shorter than giving it in first-line. And there are data collected by Paul O’Regan, on the global level at the moment, for this rechallenge. There is a study presented here at ESMO also. So, I think yes, it works. Bu, whether the magnitude of the benefit is the same, we don’t know yet.

Jeffrey Weber, MD, PhD: And so, let’s switch for a moment and let me ask you this question: do you ever discuss the “C” word with patients? Will you tell them there’s a chance for a cure with, say, immunotherapy or, if it’s a good-outcome patient, with targeted therapy?

Reinhard Dummer, MD: I don’t use the word “cure,” but I say that there’s a good chance for you that you will have a long-term benefit, and this means that you are alive at 5 years and maybe even 10 years. It’s very hard to achieve a cure and to prove that it’s a cure, but we have a good chance to have long-term control. This started with the ipilimumab data. And nowadays to be, if you say, “optimistic,” you can say that probably we can provide a 50% long-term benefit in the patient. And here, it starts with 3 years, and maybe 5 years, in the patient population. So, this is completely different. In the beginning, when I first saw the metastatic patient, we already talked a lot about palliative care and end-of-life measurement. And now I don’t feel that comfortable with this because this is not true anymore.

Jeffrey Weber, MD, PhD: Good. Well, I think we all like that. Again, if you look at the urban legend number 1: that there is a tail on the curve with immunotherapy. But now it’s not urban legend number 1, it’s reality. You, yourself, presented some of these data.

Caroline Robert, MD, PhD: You know, before when patients asked that, I told them that we had begun to have reasonable hope that we are curing some patients. So, it’s different than before. And the best illustration that there is a real hope that is shared is that young woman, when they ask for a cryopreservation of their oocytes, well, before, you know I was explaining to them in a nice way that it probably was not really worse. Because it’s not like giving sperm. It’s a little bit more complicated.

Jeffrey Weber, MD, PhD: Of course.

Caroline Robert, MD, PhD: But now we do it because we have hope that some of them will be cured. So, it’s not something that I find delirious to accept this kind of procedure.

Jeffrey Weber, MD, PhD: That’s an extraordinarily interesting thought, that we now think about the sperm donation, the oocyte donation, which we were all trained to do as oncologists when we were thinking about testicular cancer. Would we ever think about this in melanoma?

Caroline Robert, MD, PhD: I think it’s the best example that it’s changing.

Dirk Schadendorf, MD: So, usually, I’m not talking about cure, long-term benefit, and the increased likelihood that my patient is going to die from other reasons. Because there is also some other risk in life.

Caroline Robert, MD, PhD: It’s a nice way of avoiding the subject. There is a bus outside, be careful.

Axel Hauschild, MD: Honestly, when I talk about the prognosis to patients, I simply don’t use the word “cure.” And I can’t remember that patients are asking me for cure. I’m talking about now the 3- and 5-year survival data. If they are BRAF-mutated, the nice 3-year survival data—dabrafenib/trametinib, cobimetinib/vemurafenib, but also the nivolumab data—from phase I trials are 34% and saw a 5-year survival. I tell them studies, study results, and then they can estimate. But I’m very reluctant to do so if I see that the patient comes with a high tumor load and high LDH.

Jeffrey Weber, MD, PhD: Oh, yes, we all agree.

Axel Hauschild, MD: I’m not discussing it in the same way. If they have good prognostic factors, I’m telling them that they have good prognostic factors. If they have bad prognostic factors, I’m a bit more conservative.

Jeffrey Weber, MD, PhD: But the longest-term data are from CheckMate-003. That’s the Steve Hodi data presented at ASCO.

Axel Hauschild, MD: And at AACR.

Jeffrey Weber, MD, PhD: And AACR. But the question is, if you have a 35% 3-year, 34% 4-year, 35% or 34% 5-year survival, that’s a plateau. I would assume there’s a chance for a cure there.

Axel Hauschild, MD: But it’s phase I and you don’t know if it was heavily pretreated patients. These heavily pretreated patients already survived 1 to 3 lines of treatment. So, you never know. But if I see the current data for pembrolizumab, particularly the KEYNOTE-006 study, it’s the same, if not even a little bit better.

Jeffrey Weber, MD, PhD: Caroline presented the KEYNOTE-001 long-term data.

Axel Hauschild, MD: Yes, I know.

Jeffrey Weber, MD, PhD: It looks at least as good.

Caroline Robert, MD, PhD: It’s 45%.

Axel Hauschild, MD: Yes, 45%. But for first-line, it’s 50% for untreated patients.

Caroline Robert, MD, PhD: It’s 45%.

Axel Hauschild, MD: It’s 45%?

Caroline Robert, MD, PhD: It’s 45%, and for all-line, it is 40% in KEYNOTE-001.

Axel Hauschild, MD: KEYNOTE-006.

Jeffrey Weber, MD, PhD: So, those are awfully encouraging data. That says to me, maybe in the future, we can talk about cure to these patients. But no, I agree, it’s a difficult topic of conversation.

Transcript Edited for Clarity
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Transcript:

Jeffrey Weber, MD, PhD:
Have you ever given someone targeted therapy, they progressed, gone on to immunotherapy, and gone back to targeted therapy?

Caroline Robert, MD, PhD: Sure.

Reinhard Dummer, MD: Oh, yes.

Dirk Schadendorf, MD: Yes.

Axel Hauschild, MD: Yes.

Jeffrey Weber, MD, PhD: Caroline, have you done it successfully? Let me rephrase the question now.

Caroline Robert, MD, PhD: Well, I don’t have exact numbers, but we’ve done that routinely, actually. You treat, their resistance develops, you give immunotherapy, and then what do you do? You go back to targeted therapy and very often, you have a response. But it doesn’t mean that this response would last for a very long time. It depends.

Axel Hauschild, MD: My impression is that if you really expose them, or let’s say rechallenge them, they still have good response, but the response duration is much shorter than giving it in first-line. And there are data collected by Paul O’Regan, on the global level at the moment, for this rechallenge. There is a study presented here at ESMO also. So, I think yes, it works. Bu, whether the magnitude of the benefit is the same, we don’t know yet.

Jeffrey Weber, MD, PhD: And so, let’s switch for a moment and let me ask you this question: do you ever discuss the “C” word with patients? Will you tell them there’s a chance for a cure with, say, immunotherapy or, if it’s a good-outcome patient, with targeted therapy?

Reinhard Dummer, MD: I don’t use the word “cure,” but I say that there’s a good chance for you that you will have a long-term benefit, and this means that you are alive at 5 years and maybe even 10 years. It’s very hard to achieve a cure and to prove that it’s a cure, but we have a good chance to have long-term control. This started with the ipilimumab data. And nowadays to be, if you say, “optimistic,” you can say that probably we can provide a 50% long-term benefit in the patient. And here, it starts with 3 years, and maybe 5 years, in the patient population. So, this is completely different. In the beginning, when I first saw the metastatic patient, we already talked a lot about palliative care and end-of-life measurement. And now I don’t feel that comfortable with this because this is not true anymore.

Jeffrey Weber, MD, PhD: Good. Well, I think we all like that. Again, if you look at the urban legend number 1: that there is a tail on the curve with immunotherapy. But now it’s not urban legend number 1, it’s reality. You, yourself, presented some of these data.

Caroline Robert, MD, PhD: You know, before when patients asked that, I told them that we had begun to have reasonable hope that we are curing some patients. So, it’s different than before. And the best illustration that there is a real hope that is shared is that young woman, when they ask for a cryopreservation of their oocytes, well, before, you know I was explaining to them in a nice way that it probably was not really worse. Because it’s not like giving sperm. It’s a little bit more complicated.

Jeffrey Weber, MD, PhD: Of course.

Caroline Robert, MD, PhD: But now we do it because we have hope that some of them will be cured. So, it’s not something that I find delirious to accept this kind of procedure.

Jeffrey Weber, MD, PhD: That’s an extraordinarily interesting thought, that we now think about the sperm donation, the oocyte donation, which we were all trained to do as oncologists when we were thinking about testicular cancer. Would we ever think about this in melanoma?

Caroline Robert, MD, PhD: I think it’s the best example that it’s changing.

Dirk Schadendorf, MD: So, usually, I’m not talking about cure, long-term benefit, and the increased likelihood that my patient is going to die from other reasons. Because there is also some other risk in life.

Caroline Robert, MD, PhD: It’s a nice way of avoiding the subject. There is a bus outside, be careful.

Axel Hauschild, MD: Honestly, when I talk about the prognosis to patients, I simply don’t use the word “cure.” And I can’t remember that patients are asking me for cure. I’m talking about now the 3- and 5-year survival data. If they are BRAF-mutated, the nice 3-year survival data—dabrafenib/trametinib, cobimetinib/vemurafenib, but also the nivolumab data—from phase I trials are 34% and saw a 5-year survival. I tell them studies, study results, and then they can estimate. But I’m very reluctant to do so if I see that the patient comes with a high tumor load and high LDH.

Jeffrey Weber, MD, PhD: Oh, yes, we all agree.

Axel Hauschild, MD: I’m not discussing it in the same way. If they have good prognostic factors, I’m telling them that they have good prognostic factors. If they have bad prognostic factors, I’m a bit more conservative.

Jeffrey Weber, MD, PhD: But the longest-term data are from CheckMate-003. That’s the Steve Hodi data presented at ASCO.

Axel Hauschild, MD: And at AACR.

Jeffrey Weber, MD, PhD: And AACR. But the question is, if you have a 35% 3-year, 34% 4-year, 35% or 34% 5-year survival, that’s a plateau. I would assume there’s a chance for a cure there.

Axel Hauschild, MD: But it’s phase I and you don’t know if it was heavily pretreated patients. These heavily pretreated patients already survived 1 to 3 lines of treatment. So, you never know. But if I see the current data for pembrolizumab, particularly the KEYNOTE-006 study, it’s the same, if not even a little bit better.

Jeffrey Weber, MD, PhD: Caroline presented the KEYNOTE-001 long-term data.

Axel Hauschild, MD: Yes, I know.

Jeffrey Weber, MD, PhD: It looks at least as good.

Caroline Robert, MD, PhD: It’s 45%.

Axel Hauschild, MD: Yes, 45%. But for first-line, it’s 50% for untreated patients.

Caroline Robert, MD, PhD: It’s 45%.

Axel Hauschild, MD: It’s 45%?

Caroline Robert, MD, PhD: It’s 45%, and for all-line, it is 40% in KEYNOTE-001.

Axel Hauschild, MD: KEYNOTE-006.

Jeffrey Weber, MD, PhD: So, those are awfully encouraging data. That says to me, maybe in the future, we can talk about cure to these patients. But no, I agree, it’s a difficult topic of conversation.

Transcript Edited for Clarity
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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
Advances in™ Melanoma: Exploring BRAF/MEK in Adjuvant and Neoadjuvant SettingsSep 28, 20191.5
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