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Promising Immunotherapy Trials in Squamous NSCLC

Panelists: Mark A. Socinski, MD, Florida Hospital Cancer Institute; Tracey L. Evans, MD, University of Pennsylvania; David M. Jackman, MD, Dana-Farber Cancer Institute; Edward S. Kim, MD, Levine Cancer Institute; Jared Weiss, MD, UNC Lineberger Comprehensive Cancer Center
Published Online: Thursday, Mar 09, 2017



Transcript:

Mark Socinski, MD:
So, we had KEYNOTE-024, we’ve talked about that. I want to get back to Ed and just say that now that we’ve got a beachhead in first-line [therapy], over the next year or so, what do you think is coming as far as first-line immunotherapy? Is it combining? Is it other drugs are better? Or do we see the other drugs as being similar to pembrolizumab? Is it combinations with chemotherapy? Is it combinations with immunotherapy? What’s on your radar screen?

Edward S. Kim, MD: So, I’m not a predictor of future things, but it is a, obviously, very hot area, and one of rampant speculation right now. I have been very impressed with the KEYNOTE-024 data, the amount of magnitude of benefit in a PD-L1 overexpressed population. Just decades of stuff, that is probably the one thing that has changed a large amount of people in a paradigm. EGFR mutations are important, as a subset, but this is big stuff now. If we follow what happened without colleagues in melanoma and renal cell, you had a couple single agents. And then, what changed the paradigm was, in a fit patient who you felt could tolerate predictable grade 3 toxicities, the doublets occurred—the doublets being CTLA4 plus PD, PD-L1, or PD-1 inhibition.

I think that’s really an important data set that we will hopefully see over the next 6 to 12 months, what’s going to happen with the combination data—that’s the ipilimumab/nivolumab. And that parallels what we would see in melanoma. Now to David’s point, maybe it doesn’t show as great a magnitude of benefit. I think there will be benefit—again, my own sideline reporting—I just don’t know how that will stack up with toxicities on top of the magnitude of efficacy. And I think that’s where we will be back into this debate of what is appropriate for somebody, regardless of expression, because it could absolutely have nothing to do with it. Do we take that chance to get one number of efficacy versus another? And this almost sounds like IL-2, right? IL-2 is not based on certain parameters. It was based on certain efficacies where you could get some people into a near CR or that magnitude. I think that’s what we’re going to be discussing because I think the numbers will come out pretty similarly, and it’ll be based on toxicity and whether you care more about response rate, PFS, and in those terms.

And so, I think that’s what’s going to be exciting about the next year. We do have combination chemotherapy data that were presented with pembrolizumab, carboplatin, and pemetrexed. Again, that has been fast-tracked now and maybe that will be a standard in a few months, I have no idea. I think it’s still very early, but I don’t know how a community oncologist now is going to resolve testing in one setting, not test in another, and have to choose between combination chemotherapy with a drug versus single-agent because I think there’s a big reflex to that.

Mark Socinski, MD: It has been interesting that for the past year, the posturing of the immunotherapy movement has been that if we can get rid of chemotherapy, we’ll have immunotherapy. And now with the KEYNOTE-021 data, admittedly in nonsquamous, we have the FDA stepping up and saying, “Well, let’s take a look at this.” Then, we have the tremelimumab/durvalumab combination and the nivolumab/ipilimumab combination pulling back a little bit. And so, it’s interesting how life comes full cycle.

Edward S. Kim, MD: And I think we’re going to have 4 or 5 immunotherapies, which, as you alluded to before, wow. In the first-line setting, they’re all going to be tested. I don’t think they’ll all make approval there. I do think there is some value to the overexpression of PD-L1, and there are data out there that are really early and speculative looking at various populations—some in PD-L1 selected, some in not. There are atezolizumab data that are looking at SP142, which, again, you can say whether that’s a good marker or not as consistent a marker. They’re looking at tumor cells or at tumor infiltrating cells. And, again, that requires another level of sophistication that might be part of some of the issues that occur with SP142.

But I think right now, it’s too early to speculate on what’s going to end up in our first-line setting. There’s so much being tested. I’m hopeful that we do mirror how melanoma has gone, that there are combinations; again, there are the IDO (indoleamine-2,3-dioxygenase) drugs as well. Those are very less toxic, good combinations. My melanoma colleagues tell me, “Yes, we love those combinations.” So, those are things I look at.

Mark Socinski, MD: Do they work? That’s another issue. At least they’re well tolerated.

Transcript Edited for Clarity

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Transcript:

Mark Socinski, MD:
So, we had KEYNOTE-024, we’ve talked about that. I want to get back to Ed and just say that now that we’ve got a beachhead in first-line [therapy], over the next year or so, what do you think is coming as far as first-line immunotherapy? Is it combining? Is it other drugs are better? Or do we see the other drugs as being similar to pembrolizumab? Is it combinations with chemotherapy? Is it combinations with immunotherapy? What’s on your radar screen?

Edward S. Kim, MD: So, I’m not a predictor of future things, but it is a, obviously, very hot area, and one of rampant speculation right now. I have been very impressed with the KEYNOTE-024 data, the amount of magnitude of benefit in a PD-L1 overexpressed population. Just decades of stuff, that is probably the one thing that has changed a large amount of people in a paradigm. EGFR mutations are important, as a subset, but this is big stuff now. If we follow what happened without colleagues in melanoma and renal cell, you had a couple single agents. And then, what changed the paradigm was, in a fit patient who you felt could tolerate predictable grade 3 toxicities, the doublets occurred—the doublets being CTLA4 plus PD, PD-L1, or PD-1 inhibition.

I think that’s really an important data set that we will hopefully see over the next 6 to 12 months, what’s going to happen with the combination data—that’s the ipilimumab/nivolumab. And that parallels what we would see in melanoma. Now to David’s point, maybe it doesn’t show as great a magnitude of benefit. I think there will be benefit—again, my own sideline reporting—I just don’t know how that will stack up with toxicities on top of the magnitude of efficacy. And I think that’s where we will be back into this debate of what is appropriate for somebody, regardless of expression, because it could absolutely have nothing to do with it. Do we take that chance to get one number of efficacy versus another? And this almost sounds like IL-2, right? IL-2 is not based on certain parameters. It was based on certain efficacies where you could get some people into a near CR or that magnitude. I think that’s what we’re going to be discussing because I think the numbers will come out pretty similarly, and it’ll be based on toxicity and whether you care more about response rate, PFS, and in those terms.

And so, I think that’s what’s going to be exciting about the next year. We do have combination chemotherapy data that were presented with pembrolizumab, carboplatin, and pemetrexed. Again, that has been fast-tracked now and maybe that will be a standard in a few months, I have no idea. I think it’s still very early, but I don’t know how a community oncologist now is going to resolve testing in one setting, not test in another, and have to choose between combination chemotherapy with a drug versus single-agent because I think there’s a big reflex to that.

Mark Socinski, MD: It has been interesting that for the past year, the posturing of the immunotherapy movement has been that if we can get rid of chemotherapy, we’ll have immunotherapy. And now with the KEYNOTE-021 data, admittedly in nonsquamous, we have the FDA stepping up and saying, “Well, let’s take a look at this.” Then, we have the tremelimumab/durvalumab combination and the nivolumab/ipilimumab combination pulling back a little bit. And so, it’s interesting how life comes full cycle.

Edward S. Kim, MD: And I think we’re going to have 4 or 5 immunotherapies, which, as you alluded to before, wow. In the first-line setting, they’re all going to be tested. I don’t think they’ll all make approval there. I do think there is some value to the overexpression of PD-L1, and there are data out there that are really early and speculative looking at various populations—some in PD-L1 selected, some in not. There are atezolizumab data that are looking at SP142, which, again, you can say whether that’s a good marker or not as consistent a marker. They’re looking at tumor cells or at tumor infiltrating cells. And, again, that requires another level of sophistication that might be part of some of the issues that occur with SP142.

But I think right now, it’s too early to speculate on what’s going to end up in our first-line setting. There’s so much being tested. I’m hopeful that we do mirror how melanoma has gone, that there are combinations; again, there are the IDO (indoleamine-2,3-dioxygenase) drugs as well. Those are very less toxic, good combinations. My melanoma colleagues tell me, “Yes, we love those combinations.” So, those are things I look at.

Mark Socinski, MD: Do they work? That’s another issue. At least they’re well tolerated.

Transcript Edited for Clarity
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