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Treating Relapsed/Refractory NSCLC After I-O Therapy

Panelists: Leora Horn, MD, MSc, FRCPC, Vanderbilt University Medical Center; Edward B. Garon, MD, David Geffen School of Medicine at UCLA; Thomas E. Stinchcombe, MD, Duke Cancer Institute
Published: Tuesday, Oct 16, 2018



Transcript: 

Leora Horn, MD, MSc, FRCPC: Moving from the first-line setting into patients who have progressed on therapy, now that we’re using immune checkpoint inhibitors upfront, what are you doing next? For a while, all that we had were single-agent therapies. Are we back to single-agent docetaxel with or without ramucirumab? What are you offering your patients in the second-line setting once they’ve progressed on a checkpoint inhibitor?

Thomas E. Stinchcombe, MD: I think this is one of the more difficult questions to answer. Today’s successes create tomorrow’s challenges. Unfortunately, after the 3-drug combination of chemoimmunotherapy, I think the standard would be single-agent docetaxel or docetaxel with ramucirumab. Both of those have activity and are sort of validated, but they are a bit less appealing to some of our patients who come to academic centers. We’re trying to get a lot of these patients onto a clinical trial. That’s the focus. But I think single-agent chemotherapy would be the standard answer right now, unfortunately.

Leora Horn, MD, MSc, FRCPC: You’re doing a similar…

Edward B. Garon, MD: Yes, I’ve generally been using docetaxel/ramucirumab in this setting. I agree with you though. Certainly, at our centers, we tend to look at a lot of clinical trials in this setting. There is a challenge here. Patients are not that enthusiastic about these approaches. In some ways, it’s unfortunate because I do think there would be some benefit by going back to the chemotherapy-based regimen. But, it’s been tough getting them excited about it.

Leora Horn, MD, MSc, FRCPC: With the immune checkpoint inhibitors, we’ve heard a bit about those patients who are rapid or hyper-progressors. There was a subset analysis in the REVEL study. Granted, this was before we were using checkpoint inhibitors. You were the lead author and a key investigator on that study. Maybe the patients with less indolent disease who were more rapidly progressing had a better benefit with docetaxel and ramucirumab. Does the type of progression, or where they’re progressing, or how quickly they are progressing impact what you’re doing in the second-line setting?

Edward B. Garon, MD: In some of these second-line angiogenesis inhibitor studies there has been enthusiasm for looking at people who are rapidly progressing. This is a group of patients who stand to not do well. It’s also important because this is a group of patients who often don’t get treated in a setting. We now have data in secondary analyses, for instance, from REVEL, that would indicate that those patients would benefit; obviously not people whose performance status is very poor but people who either progress on initial therapy or have rapidly progressive disease. That subset clearly benefits and appears to maintain benefits that are sort of on par with what was seen in the REVEL study.

Leora Horn, MD, MSc, FRCPC: So it is something you can consider. Tom, is there a time factor? In the second-line setting, say we’ve got a squamous cell patient. We know that ramucirumab can be given in squamous and nonsquamous disease. They got their taxane and then went on maintenance pembrolizumab for 18 months. Then, they progressed. Do you think about that patient differently than the patient who progressed at 4 or 5 months? Are you going back to a platinum doublet? There is no clinical trial. How are you approaching that patient?

Thomas E. Stinchcombe, MD: This is difficult. I think that patient has a better prognosis. Most of the time they have a better performance status. I am a bit inclined to be a little more aggressive in that patient. I may think about the doublet regimen—docetaxel/ramucirumab, potentially. If the patient progresses very rapidly, I have concerns that they have a very aggressive disease and I’ve taken my best shot with the 3-drug combination. I think that’s the person for which I’m more inclined to use the single agent in. We’re going to have a conversation about prognosis and other things because I’m a bit more worried about that patient. I’ve not gone back to a platinum doublet after an interval. That’s just my practice pattern. I’m not sure if you all do that?

Edward B. Garon, MD: We had all of our management sort of settled for a while. Then, with immunotherapy, it’s sort of shaken everything up. I’ve tried not to go back to those decisions that we sort of made as a community before—not going back to platinum and those types of things. Whether that’s right or wrong, we don’t have any data. But at least to date, I’ve generally not revisited those sort of 4 versus 6 cycles of platinum. Do you bring back platinum? Do you go up to 225 mg of the taxane? Those sorts of things. I try to stick with where I was before this, at least so far.

Leora Horn, MD, MSc, FRCPC: And not to forget, the patient who gets a first-line PD-L1 [programmed cell death ligand 1] single agent—that’s a very different patient. That patient should get the platinum doublet. That’s an easier one.

Transcript Edited for Clarity 
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Transcript: 

Leora Horn, MD, MSc, FRCPC: Moving from the first-line setting into patients who have progressed on therapy, now that we’re using immune checkpoint inhibitors upfront, what are you doing next? For a while, all that we had were single-agent therapies. Are we back to single-agent docetaxel with or without ramucirumab? What are you offering your patients in the second-line setting once they’ve progressed on a checkpoint inhibitor?

Thomas E. Stinchcombe, MD: I think this is one of the more difficult questions to answer. Today’s successes create tomorrow’s challenges. Unfortunately, after the 3-drug combination of chemoimmunotherapy, I think the standard would be single-agent docetaxel or docetaxel with ramucirumab. Both of those have activity and are sort of validated, but they are a bit less appealing to some of our patients who come to academic centers. We’re trying to get a lot of these patients onto a clinical trial. That’s the focus. But I think single-agent chemotherapy would be the standard answer right now, unfortunately.

Leora Horn, MD, MSc, FRCPC: You’re doing a similar…

Edward B. Garon, MD: Yes, I’ve generally been using docetaxel/ramucirumab in this setting. I agree with you though. Certainly, at our centers, we tend to look at a lot of clinical trials in this setting. There is a challenge here. Patients are not that enthusiastic about these approaches. In some ways, it’s unfortunate because I do think there would be some benefit by going back to the chemotherapy-based regimen. But, it’s been tough getting them excited about it.

Leora Horn, MD, MSc, FRCPC: With the immune checkpoint inhibitors, we’ve heard a bit about those patients who are rapid or hyper-progressors. There was a subset analysis in the REVEL study. Granted, this was before we were using checkpoint inhibitors. You were the lead author and a key investigator on that study. Maybe the patients with less indolent disease who were more rapidly progressing had a better benefit with docetaxel and ramucirumab. Does the type of progression, or where they’re progressing, or how quickly they are progressing impact what you’re doing in the second-line setting?

Edward B. Garon, MD: In some of these second-line angiogenesis inhibitor studies there has been enthusiasm for looking at people who are rapidly progressing. This is a group of patients who stand to not do well. It’s also important because this is a group of patients who often don’t get treated in a setting. We now have data in secondary analyses, for instance, from REVEL, that would indicate that those patients would benefit; obviously not people whose performance status is very poor but people who either progress on initial therapy or have rapidly progressive disease. That subset clearly benefits and appears to maintain benefits that are sort of on par with what was seen in the REVEL study.

Leora Horn, MD, MSc, FRCPC: So it is something you can consider. Tom, is there a time factor? In the second-line setting, say we’ve got a squamous cell patient. We know that ramucirumab can be given in squamous and nonsquamous disease. They got their taxane and then went on maintenance pembrolizumab for 18 months. Then, they progressed. Do you think about that patient differently than the patient who progressed at 4 or 5 months? Are you going back to a platinum doublet? There is no clinical trial. How are you approaching that patient?

Thomas E. Stinchcombe, MD: This is difficult. I think that patient has a better prognosis. Most of the time they have a better performance status. I am a bit inclined to be a little more aggressive in that patient. I may think about the doublet regimen—docetaxel/ramucirumab, potentially. If the patient progresses very rapidly, I have concerns that they have a very aggressive disease and I’ve taken my best shot with the 3-drug combination. I think that’s the person for which I’m more inclined to use the single agent in. We’re going to have a conversation about prognosis and other things because I’m a bit more worried about that patient. I’ve not gone back to a platinum doublet after an interval. That’s just my practice pattern. I’m not sure if you all do that?

Edward B. Garon, MD: We had all of our management sort of settled for a while. Then, with immunotherapy, it’s sort of shaken everything up. I’ve tried not to go back to those decisions that we sort of made as a community before—not going back to platinum and those types of things. Whether that’s right or wrong, we don’t have any data. But at least to date, I’ve generally not revisited those sort of 4 versus 6 cycles of platinum. Do you bring back platinum? Do you go up to 225 mg of the taxane? Those sorts of things. I try to stick with where I was before this, at least so far.

Leora Horn, MD, MSc, FRCPC: And not to forget, the patient who gets a first-line PD-L1 [programmed cell death ligand 1] single agent—that’s a very different patient. That patient should get the platinum doublet. That’s an easier one.

Transcript Edited for Clarity 
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