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Using Immunotherapy Beyond Progression in NSCLC

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: Before we turn to the questions from our viewers, just briefly touch on post immunotherapy. What would you say of the role for continuing treatment beyond progression now with immunotherapy, adding to it or switching from one to another?

Gregory J. Riely, MD, PhD: I think it really depends on the kind of response you’ve got from this patient. So, if you have a patient who gets no real benefit from that immunotherapy regimen, whether it’s single agent or combination, I don’t think you should try to nurse that patient along to continue. If you see signs of progression, you never had a response, and you see new liver metastasis, I would make a change in systemic therapy.

By contrast, if you have a patient who had a tremendous response, they’re a year and a half in, and 1 new lung module has popped up, I’ve begun to address those patients like I do my patients with EGFR-mutant lung cancer. I try that oligoprogression.

Jack West, MD: OK. And then finally, would you say that there’s any meaningful difference among the checkpoint inhibitors in the second-line setting at least? I would say the data look remarkably similar considering that there are some differences that we’re seeing in the first-line setting. But I’m struck by how amazingly concordant the second-line data have been.

Gregory J. Riely, MD, PhD: I completely agree. These curves, you could put them on top of each other they’re so similar. But we have to admit that the data in the first-line setting looked different. And I guess I wonder what it tells us about how we study drugs that these data look so different. Because deep down inside, I think the drugs are the same. I think they have very similar activity, but we do see clear differences in results. Such clear differences that I’m not ready to say one is equal to another and I’m going to follow the trials to guide my prescribing, but that I wonder what’s going on.

Jared Weiss, MD: There are structural differences between the antibodies we’ve discussed today and the very other obvious difference is hitting at the PD-1 side versus the PD-L1 side. I guess the question isn’t that important to me.

Jack West, MD: And I would also say that we’ve had these agents.

Jared Weiss, MD: You know, as a clinician, I should say, Greg, I’m going to go the way the trials were done, follow the labels.

Jack West, MD: We’ve had these agents commercially available for several years, and there are a lot of people, I’m sure, who had progression on nivolumab and then tried another one. If there was meaningful efficacy of switching, we wouldn’t be debating this now. We wouldn’t have still been waiting for the 1 or 2 cases to clarify this.

Gregory J. Riely, MD, PhD: But that’s really worth highlighting.

Jared Weiss, MD: I’ll make a statement despite the absence of data. If I have a patient who has progressed on a PD-1 drug, I do not believe that there’s enough of a difference between that and other PD-1s or compared with the PD-1s—you can reverse that equation—that I would consider it a clinically reasonable approach to just switch drugs.

Jack West, MD: And that’s, I think, a great point, because people are asking, are these drugs interchangeable? I’m less confident to say that’s the case, but at the same time I’m not inclined to say that there’s some major meaningful difference between PD-1 inhibitors and PD-L1 inhibitors based on the data.

Jared Weiss, MD: That’s right. I would say though that in addition to the approach of oligo-treatment—Jack, I think you put it once this way, a few years ago at ASCO, in reference to EGFR—putting your finger over the spot on the scan if it’s not clinically relevant. I always like that way of describing it. All the same, another approach, when I look at the data showing a high response rate to chemotherapy after immunotherapy. I do not believe, and I reserve the right to be very wrong, that immunotherapy is somehow potentiating chemotherapy. I think you’re seeing residual effects still helping people. And so, when I think about that, I do think that if you stop immunotherapy because of clinically meaningful progression and you switch to something else, but you have reason to believe that there might be that lingering effect, it’s not crazy to come back to that or another drug, whatever you like at some point.

Jack West, MD: We are essentially without data on this.

Transcript Edited for Clarity 
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Transcript: 

Jack West, MD: Before we turn to the questions from our viewers, just briefly touch on post immunotherapy. What would you say of the role for continuing treatment beyond progression now with immunotherapy, adding to it or switching from one to another?

Gregory J. Riely, MD, PhD: I think it really depends on the kind of response you’ve got from this patient. So, if you have a patient who gets no real benefit from that immunotherapy regimen, whether it’s single agent or combination, I don’t think you should try to nurse that patient along to continue. If you see signs of progression, you never had a response, and you see new liver metastasis, I would make a change in systemic therapy.

By contrast, if you have a patient who had a tremendous response, they’re a year and a half in, and 1 new lung module has popped up, I’ve begun to address those patients like I do my patients with EGFR-mutant lung cancer. I try that oligoprogression.

Jack West, MD: OK. And then finally, would you say that there’s any meaningful difference among the checkpoint inhibitors in the second-line setting at least? I would say the data look remarkably similar considering that there are some differences that we’re seeing in the first-line setting. But I’m struck by how amazingly concordant the second-line data have been.

Gregory J. Riely, MD, PhD: I completely agree. These curves, you could put them on top of each other they’re so similar. But we have to admit that the data in the first-line setting looked different. And I guess I wonder what it tells us about how we study drugs that these data look so different. Because deep down inside, I think the drugs are the same. I think they have very similar activity, but we do see clear differences in results. Such clear differences that I’m not ready to say one is equal to another and I’m going to follow the trials to guide my prescribing, but that I wonder what’s going on.

Jared Weiss, MD: There are structural differences between the antibodies we’ve discussed today and the very other obvious difference is hitting at the PD-1 side versus the PD-L1 side. I guess the question isn’t that important to me.

Jack West, MD: And I would also say that we’ve had these agents.

Jared Weiss, MD: You know, as a clinician, I should say, Greg, I’m going to go the way the trials were done, follow the labels.

Jack West, MD: We’ve had these agents commercially available for several years, and there are a lot of people, I’m sure, who had progression on nivolumab and then tried another one. If there was meaningful efficacy of switching, we wouldn’t be debating this now. We wouldn’t have still been waiting for the 1 or 2 cases to clarify this.

Gregory J. Riely, MD, PhD: But that’s really worth highlighting.

Jared Weiss, MD: I’ll make a statement despite the absence of data. If I have a patient who has progressed on a PD-1 drug, I do not believe that there’s enough of a difference between that and other PD-1s or compared with the PD-1s—you can reverse that equation—that I would consider it a clinically reasonable approach to just switch drugs.

Jack West, MD: And that’s, I think, a great point, because people are asking, are these drugs interchangeable? I’m less confident to say that’s the case, but at the same time I’m not inclined to say that there’s some major meaningful difference between PD-1 inhibitors and PD-L1 inhibitors based on the data.

Jared Weiss, MD: That’s right. I would say though that in addition to the approach of oligo-treatment—Jack, I think you put it once this way, a few years ago at ASCO, in reference to EGFR—putting your finger over the spot on the scan if it’s not clinically relevant. I always like that way of describing it. All the same, another approach, when I look at the data showing a high response rate to chemotherapy after immunotherapy. I do not believe, and I reserve the right to be very wrong, that immunotherapy is somehow potentiating chemotherapy. I think you’re seeing residual effects still helping people. And so, when I think about that, I do think that if you stop immunotherapy because of clinically meaningful progression and you switch to something else, but you have reason to believe that there might be that lingering effect, it’s not crazy to come back to that or another drug, whatever you like at some point.

Jack West, MD: We are essentially without data on this.

Transcript Edited for Clarity 
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