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Pembrolizumab in Newly Diagnosed 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: Monday, Feb 27, 2017



Transcript:

Mark Socinski, MD:
So, let’s switch gears and talk a little bit about what Tracey briefly mentioned. I want to get Dr. Jackman to give us his viewpoint and summarize briefly the KEYNOTE-024 trial. I think KEYNOTE-024 had about 20% squamous patients enrolled in it. Is that correct?

David M. Jackman, MD: Yes. So, as Tracey mentioned, the KEYNOTE-024 trial was really a game-changing study. In this study, it looked specifically at patients with previously untreated metastatic non–small cell lung cancer. And it specifically looked at those whose tumors stained 50% or greater for PD-L1. And so, that’s the first piece that’s of note: how many patients are 50% or greater? When we looked at the roughly 1600 patients who had tissue that was accessible, 500 of them were positive to this degree. So, that comes out to be about 30%. That’s the first piece of significant information.

The next piece is, what happened? So, those patients were then randomized to combination chemotherapy versus pembrolizumab, a PD-1 inhibitor. And what we saw was, in terms of progression-free survival, there was benefit associated with the pembrolizumab to the extent of 10.3 months versus 6.0 months. And in terms of response rate, the response rate for the pembrolizumab-treated group was 45% versus 28%. In terms of toxicity with this new class of drugs, with these immunotherapies, people wonder, are they going to be more or less toxic compared to standard chemotherapy? What we saw was rate of toxicity across all toxicities. The pembrolizumab group had a 73% rate of some toxicity versus 90% for the combination chemotherapy. In terms of severe toxicities—what we call grade 3 to grade 5 toxicities—we saw a rate of 26% for pembrolizumab, which was about half of what we saw with the combination chemotherapy at 53%. So, overall, it associated with better efficacy and seemingly less toxicity. And so, that’s a no-brainer. If you can find a group of patients in whom to treat that you’re going to get better outcomes and less toxicity, that’s a game changer.

Mark Socinski, MD: So, I think the number was just over 1900, about 1600 tissue to test.

David M. Jackman, MD: Right.

Mark Socinski, MD: Yet, we actually ended up with about 305, I think, being randomized. So, when this gets out to Main Street USA, this is not for every patient, right? It’s going to end up, in my opinion, being in the 10%-to-20% of range, assuming that physicians are testing on a routine basis. Right?

David M. Jackman, MD: That’s right. And then, again, obviously adding back to what Jared had mentioned about, are they doing the correct test? How do you interpret it if they’re using VENTANA assay? Can you draw parallels?

Mark Socinski, MD: I don’t know. I think it remains to be seen. Are people going to demand that if you’re going to use pembrolizumab first-line, that it has to be linked to the Merck test? Or are you just PD-L1–positive?

Jared Weiss, MD: Well, we have recent history on that strain. If you have an ALK patient and you get next-generation sequencing that shows the ALK, you can use crizotinib. I don’t know of a major payer in the country that says, “No, you didn’t get the FISH assay.” I suspect it’s going to be the same here.

Mark Socinski, MD: I would suspect it would be the same, and I think it should be the same based on what we know about at least those 3 antibodies. So, David, new standard of care?

David M. Jackman, MD: Absolutely.

Mark Socinski, MD: In this population. Does anyone disagree with that?

Edward S. Kim, MD: Yes. I think it’s the first time that we’re finally following a breast paradigm with HER2. This is, I think, the closest thing that exists to that model. And I got a little concerned when I heard people with EGFR mutations in the past say, “Well, I can test later” or “I don’t have to test because I’m going to get it second-line.” Again, the same argument exists. Not 100% of patients get second-line therapy in lung cancer. And you would feel bad if you had a patient who was 80% PD-L1–positive. I just saw a lady who was 78 years old and she had 80% PD-L1–positivity. She looked 78 years old. It was not one of these 78-year-olds who looked 60. She just came back after 3 cycles of pembrolizumab and had 80% shrinkage of her tumor. It’s unbelievable, and maybe she would have done very well on chemotherapy as well, but I’m glad that she was able to take a drug that she tolerated very well as a single agent, that is more of a targeted or directed therapy as opposed to general chemotherapy.

Tracey L. Evans, MD: To build on that, in the setting of the targeted agents, all those randomized studies against chemotherapy showed the same survival. So, even though you’re doing your patient a favor by giving them a targeted agent first, in terms of toxicity, you are not causing a detriment to their overall survival if you started with chemotherapy. But that’s the case here with immunotherapy, even though these patients were treated in a time when second-line therapy was available. They had an overall survival benefit by getting the immunotherapy first. They were not necessarily salvageable in the second-line setting.

Jared Weiss, MD: I think some of these patients are a little bit sicker compared to the typical EGFR-mutated patient. And I think it’s a very real number. Because of those coexisting morbidities and their age, they are not going to get second-line much more so than the EGFR/ALK experience.

Edward S. Kim, MD: And they see Jimmie Carter out there watching the Atlanta Falcons game and out there building houses for Habitat for Humanity, but he’s getting pembrolizumab right now for melanoma; clearly, a tolerability aspect is right in front of them.

Transcript Edited for Clarity

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Transcript:

Mark Socinski, MD:
So, let’s switch gears and talk a little bit about what Tracey briefly mentioned. I want to get Dr. Jackman to give us his viewpoint and summarize briefly the KEYNOTE-024 trial. I think KEYNOTE-024 had about 20% squamous patients enrolled in it. Is that correct?

David M. Jackman, MD: Yes. So, as Tracey mentioned, the KEYNOTE-024 trial was really a game-changing study. In this study, it looked specifically at patients with previously untreated metastatic non–small cell lung cancer. And it specifically looked at those whose tumors stained 50% or greater for PD-L1. And so, that’s the first piece that’s of note: how many patients are 50% or greater? When we looked at the roughly 1600 patients who had tissue that was accessible, 500 of them were positive to this degree. So, that comes out to be about 30%. That’s the first piece of significant information.

The next piece is, what happened? So, those patients were then randomized to combination chemotherapy versus pembrolizumab, a PD-1 inhibitor. And what we saw was, in terms of progression-free survival, there was benefit associated with the pembrolizumab to the extent of 10.3 months versus 6.0 months. And in terms of response rate, the response rate for the pembrolizumab-treated group was 45% versus 28%. In terms of toxicity with this new class of drugs, with these immunotherapies, people wonder, are they going to be more or less toxic compared to standard chemotherapy? What we saw was rate of toxicity across all toxicities. The pembrolizumab group had a 73% rate of some toxicity versus 90% for the combination chemotherapy. In terms of severe toxicities—what we call grade 3 to grade 5 toxicities—we saw a rate of 26% for pembrolizumab, which was about half of what we saw with the combination chemotherapy at 53%. So, overall, it associated with better efficacy and seemingly less toxicity. And so, that’s a no-brainer. If you can find a group of patients in whom to treat that you’re going to get better outcomes and less toxicity, that’s a game changer.

Mark Socinski, MD: So, I think the number was just over 1900, about 1600 tissue to test.

David M. Jackman, MD: Right.

Mark Socinski, MD: Yet, we actually ended up with about 305, I think, being randomized. So, when this gets out to Main Street USA, this is not for every patient, right? It’s going to end up, in my opinion, being in the 10%-to-20% of range, assuming that physicians are testing on a routine basis. Right?

David M. Jackman, MD: That’s right. And then, again, obviously adding back to what Jared had mentioned about, are they doing the correct test? How do you interpret it if they’re using VENTANA assay? Can you draw parallels?

Mark Socinski, MD: I don’t know. I think it remains to be seen. Are people going to demand that if you’re going to use pembrolizumab first-line, that it has to be linked to the Merck test? Or are you just PD-L1–positive?

Jared Weiss, MD: Well, we have recent history on that strain. If you have an ALK patient and you get next-generation sequencing that shows the ALK, you can use crizotinib. I don’t know of a major payer in the country that says, “No, you didn’t get the FISH assay.” I suspect it’s going to be the same here.

Mark Socinski, MD: I would suspect it would be the same, and I think it should be the same based on what we know about at least those 3 antibodies. So, David, new standard of care?

David M. Jackman, MD: Absolutely.

Mark Socinski, MD: In this population. Does anyone disagree with that?

Edward S. Kim, MD: Yes. I think it’s the first time that we’re finally following a breast paradigm with HER2. This is, I think, the closest thing that exists to that model. And I got a little concerned when I heard people with EGFR mutations in the past say, “Well, I can test later” or “I don’t have to test because I’m going to get it second-line.” Again, the same argument exists. Not 100% of patients get second-line therapy in lung cancer. And you would feel bad if you had a patient who was 80% PD-L1–positive. I just saw a lady who was 78 years old and she had 80% PD-L1–positivity. She looked 78 years old. It was not one of these 78-year-olds who looked 60. She just came back after 3 cycles of pembrolizumab and had 80% shrinkage of her tumor. It’s unbelievable, and maybe she would have done very well on chemotherapy as well, but I’m glad that she was able to take a drug that she tolerated very well as a single agent, that is more of a targeted or directed therapy as opposed to general chemotherapy.

Tracey L. Evans, MD: To build on that, in the setting of the targeted agents, all those randomized studies against chemotherapy showed the same survival. So, even though you’re doing your patient a favor by giving them a targeted agent first, in terms of toxicity, you are not causing a detriment to their overall survival if you started with chemotherapy. But that’s the case here with immunotherapy, even though these patients were treated in a time when second-line therapy was available. They had an overall survival benefit by getting the immunotherapy first. They were not necessarily salvageable in the second-line setting.

Jared Weiss, MD: I think some of these patients are a little bit sicker compared to the typical EGFR-mutated patient. And I think it’s a very real number. Because of those coexisting morbidities and their age, they are not going to get second-line much more so than the EGFR/ALK experience.

Edward S. Kim, MD: And they see Jimmie Carter out there watching the Atlanta Falcons game and out there building houses for Habitat for Humanity, but he’s getting pembrolizumab right now for melanoma; clearly, a tolerability aspect is right in front of them.

Transcript Edited for Clarity
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