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Managing the IMpower 150 Regimen in Nonsquamous mNSCLC

Insights From: Hossein Borghaei, DO, Fox Chase Cancer Center; Corey J. Langer, MD, Perelman School of Medicine; Vassiliki Papadimitrakopoulou, MD, MD Anderson Cancer Center
Published: Monday, Aug 06, 2018



Transcript: 

Hossein Borghaei, DO: To me, yes, there were more toxicities with the quadruplet combination, but we all knew that carboplatin/paclitaxel/bevacizumab can have additional toxicities when you add a fourth drug to it. I don’t think there were any new safety signals that were alarming because of this combination, but it was definitely slightly more toxicity. Compare that with a triplet combination of carboplatin, pemetrexed, and pembrolizumab, and there was slightly less toxicity. But every time you add a new drug, that brings with it additional toxicities. We have to emphasize that what we see has been in line with what we have been expecting from all these combinations. But you have to decide if that patient sitting across from you is an appropriate candidate for the quadruplet combination or if the triplet combination is sufficient.

I think the other way to look at it is that now we have all these options for patients with nonsquamous histology. You can use carboplatin, paclitaxel, and bevacizumab if that’s what you’ve been working with. On the other hand, if that’s not something you want to use, a carboplatin/pemetrexed backbone can easily be adopted for the majority of patients we see. Again, you have all those options. Then you bring in CheckMate-227. It’s very hard for us to do a cross-trial comparison because of the different patient population, but you see that the combination of ipilimumab plus nivolumab has roughly 25% grade 3 or 4 toxicities. In an appropriate patient with a high TMB, maybe that would be another option that you have to try. I don’t think I’ve seen anything that would tell me I definitely would not want to use one of these combinations. It’s just that you have to be aware that, yes, you’re going to have to deal with additional toxicities.

Corey J. Langer, MD: Atezolizumab, like pembrolizumab, can add immune-mediated toxicities to the typical chemotherapy or chemotherapy/angiogenesis inhibitor regimen. Beyond that, there really aren’t other major toxicity concerns. It should be noted that roughly a third of patients ultimately stop treatment at some point because of adverse events—not necessarily grade 3 or 4 adverse events, but because of some sort of side effect—compared with 25% in the control group, the paclitaxel/carboplatin/bevacizumab arm. Intriguingly, only 13% or 14% stopped in the atezolizumab arm. So, in direct comparison, the implication is that atezolizumab may have a bit less toxicity than bevacizumab in this setting, but I think that may be overinterpreting some of the data. In large part, this regimen of 4 separate drugs, although it’s quite comprehensive, is manageable. The toxicity is typical of what we’d expect. There are no major surprises.

Transcript Edited for Clarity 
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Transcript: 

Hossein Borghaei, DO: To me, yes, there were more toxicities with the quadruplet combination, but we all knew that carboplatin/paclitaxel/bevacizumab can have additional toxicities when you add a fourth drug to it. I don’t think there were any new safety signals that were alarming because of this combination, but it was definitely slightly more toxicity. Compare that with a triplet combination of carboplatin, pemetrexed, and pembrolizumab, and there was slightly less toxicity. But every time you add a new drug, that brings with it additional toxicities. We have to emphasize that what we see has been in line with what we have been expecting from all these combinations. But you have to decide if that patient sitting across from you is an appropriate candidate for the quadruplet combination or if the triplet combination is sufficient.

I think the other way to look at it is that now we have all these options for patients with nonsquamous histology. You can use carboplatin, paclitaxel, and bevacizumab if that’s what you’ve been working with. On the other hand, if that’s not something you want to use, a carboplatin/pemetrexed backbone can easily be adopted for the majority of patients we see. Again, you have all those options. Then you bring in CheckMate-227. It’s very hard for us to do a cross-trial comparison because of the different patient population, but you see that the combination of ipilimumab plus nivolumab has roughly 25% grade 3 or 4 toxicities. In an appropriate patient with a high TMB, maybe that would be another option that you have to try. I don’t think I’ve seen anything that would tell me I definitely would not want to use one of these combinations. It’s just that you have to be aware that, yes, you’re going to have to deal with additional toxicities.

Corey J. Langer, MD: Atezolizumab, like pembrolizumab, can add immune-mediated toxicities to the typical chemotherapy or chemotherapy/angiogenesis inhibitor regimen. Beyond that, there really aren’t other major toxicity concerns. It should be noted that roughly a third of patients ultimately stop treatment at some point because of adverse events—not necessarily grade 3 or 4 adverse events, but because of some sort of side effect—compared with 25% in the control group, the paclitaxel/carboplatin/bevacizumab arm. Intriguingly, only 13% or 14% stopped in the atezolizumab arm. So, in direct comparison, the implication is that atezolizumab may have a bit less toxicity than bevacizumab in this setting, but I think that may be overinterpreting some of the data. In large part, this regimen of 4 separate drugs, although it’s quite comprehensive, is manageable. The toxicity is typical of what we’d expect. There are no major surprises.

Transcript Edited for Clarity 
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