Continuing/Re-Challenging With I-O Therapy in NSCLC



Leora Horn, MD, MSc, FRCPC: What about continuing immunotherapy beyond progression? This is a question that comes up a lot for patients who come through my clinic. They’re on a checkpoint inhibitor and slowly start to progress or progress in 1 or 2 sites. Do you keep that immunotherapy agent going and add something? Do you stop the immunotherapy agent? Do you switch to something different? How do you approach those patients?

Edward B. Garon, MD: In general, in my practice, when somebody progresses on an agent we have always said that the agent is no longer working. I really haven’t seen data that has dissuaded me from that. The largest data set with atezolizumab was really looked at in the OAK study. They looked at patients who continued beyond progression. I believe the response rate was about 7% in that analysis. That said, there are all sorts of questions that come up. This is only a subset of patients that the practitioner felt were doing well enough to continue. There may have been some cases in which the practitioner said they met the RECIST [Response Evaluation Criteria in Solid Tumors] criteria for progression when, in fact, they were not truly having a problem. The other thing to consider is whether that’s even a valid radiographic tool. With RECIST, once you’ve progressed, you’ve progressed. And so, how one can even define what a response is, at that point, is a bit difficult.

The other thing, again, is, when you do look at something like the docetaxel/ramucirumab data, and this is taking a different study, the response rate was 23%. That’s not saying that you would get a 23% response if you took those people who were doing well on atezolizumab and chose to continue. But, if you use that metric, that 7% is not such a home run.

Leora Horn, MD, MSc, FRCPC: One of the things that I see in my clinic, and I don’t know if you’ve seen it but it’s out there, is that patients who are on a checkpoint inhibitor and get subsequent chemotherapy seem to do a lot better on that subsequent chemotherapy. I admittedly use a lower dose of docetaxel. I don’t use the 75 mg/m2-dose. I use 60 mg/m2. I find that 75 mg/m2 is hard to give. And so, there are options beyond progression. What do you do for the patient, Tom, who stops and then progress 6 or 8 months later; or they were on chemotherapy and progressed? Do you ever go back to an immunotherapy agent? This would be opposed to a case where they’re on it and they’re progressing, in which Eddie said you stop.

Thomas E. Stinchcombe, MD: I’ve had a few patients who have gone through 2 years of pembrolizumab. And then, when we observe them, there might be some growth. Generally, I’ve just started them as a fresh start. For a very short time after stopping the immunotherapy I’m a bit more skeptical and hesitant about going back to the immunotherapy. I’d like to see a 6- to 12-month treatment-free interval before going back.

Leora Horn, MD, MSc, FRCPC: Are they responding, or are you seeing what we saw in CheckMate-153, where many of the patients who stopped at 1 year and then re-challenged did not re-respond?

Thomas E. Stinchcombe, MD: I have to be honest, it’s only a handful. In some of them, I’ve done the carboplatin platinum therapy.

Leora Horn, MD, MSc, FRCPC: OK, so it’s hard to know what the response is from.

Thomas E. Stinchcombe, MD: Yes. I do this when the patient has a really good performance status and is asymptomatic. Again, it’s only a handful of patients. I don’t really know how to manage these situations, to be honest with you.

Leora Horn, MD, MSc, FRCPC: How about you?

Edward B. Garon, MD: I must admit that I’ve probably been more aggressive about maintaining the PD-1 [programmed cell death 1] inhibitor than almost all of my colleagues. I think there are 2 inputs that go into that. The study we were most involved in was the KEYNOTE-001 study. That study treated forever. We now have people who are on year 7 of pembrolizumab. Do those people need pembrolizumab at this point? I have no idea. We were also involved in CheckMate-153, which raises concerns about restarting.

The 1 additional thing that I would say is that, in my mind, there are 2 different types of progression that we see with immunotherapy. One is the traditional progression we used to see with docetaxel, where all of the disease was getting worse. We definitely see a significant percentage of patients who are clearly progressing by RECIST data, who are really progressing at a single site. In those situations, I have been fairly aggressive about treating with radiation or radiofrequency ablation, or other locally ablative approaches. Many of those patients have continued to do well for long periods of time.

Leora Horn, MD, MSc, FRCPC: And then, do you continue the pembrolizumab or whatever they were on, like atezolizumab and nivolumab, at that point?

Edward B. Garon, MD: I have generally continued patients who were on it. Interestingly, in patients who may have suffered from a toxicity that led me to stop it I’ve generally not resumed it. Often, they do very well for long periods of time with no other problematic lesions.

Thomas E. Stinchcombe, MD: It was really challenging because you are sort of trying to figure out if it is related to the disease or the treatment. You have a very small data set to work from, individually.

Leora Horn, MD, MSc, FRCPC: Yes, we have some of those patients. Surgeons have gone in, operated, and described—it’s also out there in the literature—that when they operate on those patients their lungs are almost like the lungs of radiation patients. They’re very hard and fibrotic. But we also, depending on where they’ve progressed, look at plucking it out. First, we biopsy to make sure that it’s actually progression, because we’ve been fooled once or twice into thinking that it’s granulomatous disease or something else.

Transcript Edited for Clarity

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