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Important Data in the Squamous NSCLC Population

Panelists: Jack West, MD, Swedish Cancer Institute; Gregory J. Riely, MD, PhD, Memorial Sloan Kettering Cancer Center; Jared Weiss, MD, UNC School of Medicine; Charu Aggarwal, MD, MPH, University of Pennsylvania Hospital
Published: Monday, Jul 23, 2018



Transcript: 

Jack West, MD: Let’s move on, because we’ve been talking about the importance of KEYNOTE-189 in the nonsquamous population. One of the, I would say, sleeper presentations at ASCO—because we didn’t have the data for it until just before the meeting itself and so the ASCO program committee couldn’t feature it as they otherwise would have—was the trial, KEYNOTE-407, which was a randomized phase III study of advanced squamous non–small cell lung cancer with any level of PD-L1, randomizing patients to carboplatin and nab-paclitaxel or standard solvent-based paclitaxel with either placebo or pembrolizumab. So, really very similar to the KEYNOTE-189 trial except in a squamous population with a different chemotherapy backbone.

And the trial results looked, I would say, every bit as impressive as KEYNOTE-189. Before late May, all we had heard was that there was a response rate difference, which in itself didn’t impress me that much, except in the abstract it was a 23% difference, which is enough to get noticed. But it also had a major, huge difference in progression-free survival and overall survival, both in the broad population and in all of the different subgroups across the spectrum—from PD-L1 less than 1% to low and then the highs—and again leading to the question of, what might you do with various options for the highs, etc? But I would say without any real surprises for toxicity and with very comparable results and benefits for nab-paclitaxel versus paclitaxel, this became a clear standard and a very attractive option for these patients who were not strong candidates for monotherapy with high PD-L1. But there was another squamous trial that I thought would end up being kind of a showdown between the two. I would say in the end, not so much. Can you tell us, Greg, about IMpower131?

Gregory J. Riely, MD, PhD: Right. So, this trial was very much the analogous trial looking at the backbone of carboplatin and a taxane and adding atezolizumab. The trial was somewhat more complicated in design—so, 3 arms rather than 2—but it asked the same question. As you did, I expected to see the same answer. But we didn’t see the same answer. The progression-free survival was improved, but on the initial analysis, there was no improvement in overall survival when we looked at platinum/taxane/atezolizumab. And so, as a consequence, it was a disappointment, even though other years we might have thought this was a practice-changing trial. But in the presence of the pembrolizumab data that said that you could get a better progression-free survival and overall survival, I think it’s hard to say that these atezolizumab trials really guide us.

Jack West, MD: Right. Again, it’s encouraging that there’s clearly a pattern here of chemo-immunotherapy being superior. But one of my thoughts in the wake of AACR, where you had the KEYNOTE-189 trial with a survival benefit and then CheckMate-227 with the PFS, but not OS, I thought, you don’t bring a knife to a gunfight, you don’t bring PFS to an OS fight. And I think if you have competing options and one delivers the big OS benefit, that’s going to get the nod in my mind.

Charu Aggarwal, MD, MPH: What’s really striking from these trials is that these are patients with squamous histology. They’re usually older, tougher to treat, they don’t have targeted mutation, and yet we’re seeing hazard ratios in the 0.6 range for the first time. And I think it’s a very gratifying time to be a lung cancer doctor because of, now, the power of triplet therapy.

Jack West, MD: Absolutely. The fact that there now is, we’re trying to revise the NCCN guidelines to be up-to-date and all these other things. To think that we would be arguing over competing positive phase III trials is a place where it was really hard to envision us being 10 years ago, when it seems like you could be ‘O’ for ASCO in lung cancer.

Transcript Edited for Clarity
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Transcript: 

Jack West, MD: Let’s move on, because we’ve been talking about the importance of KEYNOTE-189 in the nonsquamous population. One of the, I would say, sleeper presentations at ASCO—because we didn’t have the data for it until just before the meeting itself and so the ASCO program committee couldn’t feature it as they otherwise would have—was the trial, KEYNOTE-407, which was a randomized phase III study of advanced squamous non–small cell lung cancer with any level of PD-L1, randomizing patients to carboplatin and nab-paclitaxel or standard solvent-based paclitaxel with either placebo or pembrolizumab. So, really very similar to the KEYNOTE-189 trial except in a squamous population with a different chemotherapy backbone.

And the trial results looked, I would say, every bit as impressive as KEYNOTE-189. Before late May, all we had heard was that there was a response rate difference, which in itself didn’t impress me that much, except in the abstract it was a 23% difference, which is enough to get noticed. But it also had a major, huge difference in progression-free survival and overall survival, both in the broad population and in all of the different subgroups across the spectrum—from PD-L1 less than 1% to low and then the highs—and again leading to the question of, what might you do with various options for the highs, etc? But I would say without any real surprises for toxicity and with very comparable results and benefits for nab-paclitaxel versus paclitaxel, this became a clear standard and a very attractive option for these patients who were not strong candidates for monotherapy with high PD-L1. But there was another squamous trial that I thought would end up being kind of a showdown between the two. I would say in the end, not so much. Can you tell us, Greg, about IMpower131?

Gregory J. Riely, MD, PhD: Right. So, this trial was very much the analogous trial looking at the backbone of carboplatin and a taxane and adding atezolizumab. The trial was somewhat more complicated in design—so, 3 arms rather than 2—but it asked the same question. As you did, I expected to see the same answer. But we didn’t see the same answer. The progression-free survival was improved, but on the initial analysis, there was no improvement in overall survival when we looked at platinum/taxane/atezolizumab. And so, as a consequence, it was a disappointment, even though other years we might have thought this was a practice-changing trial. But in the presence of the pembrolizumab data that said that you could get a better progression-free survival and overall survival, I think it’s hard to say that these atezolizumab trials really guide us.

Jack West, MD: Right. Again, it’s encouraging that there’s clearly a pattern here of chemo-immunotherapy being superior. But one of my thoughts in the wake of AACR, where you had the KEYNOTE-189 trial with a survival benefit and then CheckMate-227 with the PFS, but not OS, I thought, you don’t bring a knife to a gunfight, you don’t bring PFS to an OS fight. And I think if you have competing options and one delivers the big OS benefit, that’s going to get the nod in my mind.

Charu Aggarwal, MD, MPH: What’s really striking from these trials is that these are patients with squamous histology. They’re usually older, tougher to treat, they don’t have targeted mutation, and yet we’re seeing hazard ratios in the 0.6 range for the first time. And I think it’s a very gratifying time to be a lung cancer doctor because of, now, the power of triplet therapy.

Jack West, MD: Absolutely. The fact that there now is, we’re trying to revise the NCCN guidelines to be up-to-date and all these other things. To think that we would be arguing over competing positive phase III trials is a place where it was really hard to envision us being 10 years ago, when it seems like you could be ‘O’ for ASCO in lung cancer.

Transcript Edited for Clarity
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