Select Topic:
Browse by Series:

Duration of Upfront Immunotherapy for NSCLC

Panelists: Everett Vokes, MD, University of Chicago Medicine and Biological Sciences; Roy Herbst, MD, PhD, Yale Cancer Center; Fred Hirsch, MD, PhD, University of Colorado School of Medicine; Suresh Ramalingam, MD, Winship Cancer Institute Emory University; Naiyer Rizvi, MD, Columbia University Medical Center
Published: Thursday, Sep 28, 2017



Transcript: 

Everett Vokes, MD: We’ve covered a lot of the key studies. There are a lot of unanswered questions, of course. We covered where PD-L1-negative or low expressers fall into this, and we’re waiting for more data. Another issue is the duration of therapy and how long to go with that. We talked, early on—you had a patient who’s now in year 8, and presumably, not on maintenance therapy, at this point?

Suresh Ramalingam, MD: No, he was on the initial phase I trial, and all those trials stopped therapy at 2 years.

Everett Vokes, MD: And so, we all have that experience. What do you think are the guidelines? Are there data that we can use to inform us, at this point? Naiyer?

Naiyer Rizvi, MD: I think we don’t know the duration of therapy. There was some data from The European Society for Medical Oncology (ESMO) 2017 Congress, such as a trial called CheckMate153, that looked at (in the pretreated patient population) nivolumab for 1 year versus nivolumab given on an indefinite basis. I was actually surprised to see the progression-free survival was considerably better with the indefinite versus the 1-year group. Keep in mind that this trial was not statistically powered to answer that question. It’s really more of a safety trial, and there wasn’t an overall survival difference. Nevertheless, I think it validated to at least continue these therapies beyond just 3 or 4 doses.

My general practice is that for those infrequent patients that have a complete response, I’ll often continue them for 6 months beyond complete response, and stop at that point. There’s good data from the melanoma literature with pembrolizumab that if you do that, the durability is nearly 100%. Otherwise, I tend to treat patients for 2 years and stop at that point. For patients that have moderately severe toxicity, or cumulative toxicity, and they’ve had a good response, I’ll stop it earlier. For the patients that are having significant side effects, I don’t think you need to keep going. I think that it’s probably okay to stop.

Everett Vokes, MD: I think there will be a lot of very interesting discussions around this as we go on discussing adjuvant therapies and how long they should continue. Or, another item might be the relevance of this information for induction chemotherapy, where we usually give a very short segment of the trial drug—maybe that’s not enough and we would have to continue?

Talking a little bit more about this combination of chemotherapy and pembrolizumab, the toxicity between those 2, you would, in theory at least, be worried that there would be an interaction. What was the clinical experience?

Suresh Ramalingam, MD: The good news is that the combination of chemotherapy and checkpoint inhibition seems to be well-tolerated. When you look at the toxicity differences in detail, fatigue comes up as being slightly more common with the immune checkpoint chemotherapy combination. You also, then, see some immune-related adverse events. Most of them tend to be grade 1 or 2, where you can manage through or proactively recognize and make sure they are mitigated with whatever we do next to these patients. So, from my perspective, the combination has been overall well-tolerated and seems to be a safe approach for patients. When the phase III trials read out, we’ll have even stronger information on that topic.

Everett Vokes, MD: At this point, we see single-component toxicities, but nothing that’s somehow synergistically adding more?

Suresh Ramalingam, MD: That’s correct.

Everett Vokes, MD: Have you actually treated patients with this combination?

Suresh Ramalingam, MD: I have. Now that it’s on label, when we discuss treatment options with patients, we’re talking to them about this as being a potential treatment option. And the patients that I’ve talked to have all wanted to go for that approach. In the past few weeks, I’ve treated 3 or 4 patients, now, with the combination. I’ve been pleased with at least the safety, so far. It’s a little too soon to know anything about the effectiveness in those patients.

Everett Vokes, MD: Fred, have you treated patients with the combination?

Fred Hirsch, MD, PhD: No I have not.

Everett Vokes, MD: You’re waiting. And Naiyer?

Fred Hirsch, MD, PhD: Yes.

Naiyer Rizvi, MD: For cases where there’s patients who are pretty symptomatic and have a fair amount of disease, you need a more rapid response. I’ve used it a few times, but not consistently. I tend to prioritize some of the immunotherapy combinations that would be trial options for patients if they progress on chemotherapy. I think that that’s been my bias.

Transcript Edited for Clarity 

Slider Left
Slider Right


Transcript: 

Everett Vokes, MD: We’ve covered a lot of the key studies. There are a lot of unanswered questions, of course. We covered where PD-L1-negative or low expressers fall into this, and we’re waiting for more data. Another issue is the duration of therapy and how long to go with that. We talked, early on—you had a patient who’s now in year 8, and presumably, not on maintenance therapy, at this point?

Suresh Ramalingam, MD: No, he was on the initial phase I trial, and all those trials stopped therapy at 2 years.

Everett Vokes, MD: And so, we all have that experience. What do you think are the guidelines? Are there data that we can use to inform us, at this point? Naiyer?

Naiyer Rizvi, MD: I think we don’t know the duration of therapy. There was some data from The European Society for Medical Oncology (ESMO) 2017 Congress, such as a trial called CheckMate153, that looked at (in the pretreated patient population) nivolumab for 1 year versus nivolumab given on an indefinite basis. I was actually surprised to see the progression-free survival was considerably better with the indefinite versus the 1-year group. Keep in mind that this trial was not statistically powered to answer that question. It’s really more of a safety trial, and there wasn’t an overall survival difference. Nevertheless, I think it validated to at least continue these therapies beyond just 3 or 4 doses.

My general practice is that for those infrequent patients that have a complete response, I’ll often continue them for 6 months beyond complete response, and stop at that point. There’s good data from the melanoma literature with pembrolizumab that if you do that, the durability is nearly 100%. Otherwise, I tend to treat patients for 2 years and stop at that point. For patients that have moderately severe toxicity, or cumulative toxicity, and they’ve had a good response, I’ll stop it earlier. For the patients that are having significant side effects, I don’t think you need to keep going. I think that it’s probably okay to stop.

Everett Vokes, MD: I think there will be a lot of very interesting discussions around this as we go on discussing adjuvant therapies and how long they should continue. Or, another item might be the relevance of this information for induction chemotherapy, where we usually give a very short segment of the trial drug—maybe that’s not enough and we would have to continue?

Talking a little bit more about this combination of chemotherapy and pembrolizumab, the toxicity between those 2, you would, in theory at least, be worried that there would be an interaction. What was the clinical experience?

Suresh Ramalingam, MD: The good news is that the combination of chemotherapy and checkpoint inhibition seems to be well-tolerated. When you look at the toxicity differences in detail, fatigue comes up as being slightly more common with the immune checkpoint chemotherapy combination. You also, then, see some immune-related adverse events. Most of them tend to be grade 1 or 2, where you can manage through or proactively recognize and make sure they are mitigated with whatever we do next to these patients. So, from my perspective, the combination has been overall well-tolerated and seems to be a safe approach for patients. When the phase III trials read out, we’ll have even stronger information on that topic.

Everett Vokes, MD: At this point, we see single-component toxicities, but nothing that’s somehow synergistically adding more?

Suresh Ramalingam, MD: That’s correct.

Everett Vokes, MD: Have you actually treated patients with this combination?

Suresh Ramalingam, MD: I have. Now that it’s on label, when we discuss treatment options with patients, we’re talking to them about this as being a potential treatment option. And the patients that I’ve talked to have all wanted to go for that approach. In the past few weeks, I’ve treated 3 or 4 patients, now, with the combination. I’ve been pleased with at least the safety, so far. It’s a little too soon to know anything about the effectiveness in those patients.

Everett Vokes, MD: Fred, have you treated patients with the combination?

Fred Hirsch, MD, PhD: No I have not.

Everett Vokes, MD: You’re waiting. And Naiyer?

Fred Hirsch, MD, PhD: Yes.

Naiyer Rizvi, MD: For cases where there’s patients who are pretty symptomatic and have a fair amount of disease, you need a more rapid response. I’ve used it a few times, but not consistently. I tend to prioritize some of the immunotherapy combinations that would be trial options for patients if they progress on chemotherapy. I think that that’s been my bias.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 18th Annual International Lung Cancer Congress®Oct 31, 20181.5
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
Publication Bottom Border
Border Publication
x