New Paradigms for Treatment of Locally Advanced NSCLC - Episode 8
Mark Kris, MD: Obviously, we’re all using this regimen. Are there any tips, that you’d like to share? Have any special issues come up, so far, in your treatment of this new paradigm? This is a pretty quick change. Only 6 months ago, we weren’t doing this. Now, we are. Have you learned anything in the last 6 months?
Walter J. Curran Jr., MD: I think the important thing to learn, from the trial, first, is that the adverse event profiles were only slightly different between the placebo arm and the durvalumab arm. As you were saying, when you’re going for a curative endpoint, you’re willing to sometimes put up with worse toxicities. The toxicities, as reported, were not significantly worse. I think that surprised a lot of people.
Mark Kris, MD: Yes, I think it did.
Walter J. Curran Jr., MD: Right now, the same guidelines that people are using to deal with any of the checkpoint inhibitors and their toxicities would apply. I’ve not heard of any unusual effects in this cohort, as opposed to those getting this treatment for metastatic disease.
Mark Kris, MD: Let’s say you have a medical oncologist who wanted to give 4 cycles of chemotherapy (their standard)? They’re unconvinced by this data, so far. What would you say to that medical oncologist?
Walter J. Curran Jr., MD: You’re saying that he or she wants to give the 4 cycles with the radiation, rather than give durvalumab?
Mark Kris, MD: Yes.
Walter J. Curran Jr., MD: I would push for using durvalumab. Once we have survival data and longer progression-free survival, I would even push harder.
Mark Kris, MD: OK. Jyoti, have you learned anything, in the last 6 months, from doing this?
Jyoti D. Patel, MD: I think this study is certainly singular. It changes the paradigm. But getting back to something that Walter mentioned, there is now an accumulating body of data that suggest that there is synergism between radiation and immunotherapy. We’re seeing these subsets do better than ever before. And so, although it’s 1 study, it kind of stands on the shoulders of a large body of data that really supports this concept.
Mark Kris, MD: One issue that has come up, already, is, what do you do when somebody has pneumonitis? I was faced with that. We had 2 competing causes. Easily, it could have happened from the concurrent chemotherapy and radiation. But it could also occur in a patient who is on an immune checkpoint blockade, as well. The treatment, for both, is the same. So, that made it easier. But it was quite a dilemma.
Walter J. Curran Jr., MD: The question is whether you’d stop the immune checkpoint or not. That’s the toughest part.
Mark Kris, MD: Right. That was the exact question that came up. One interesting thing, though, is that a growing source of literature suggests that patients—often, with the most profound benefits from immune checkpoint blockade, that have very serious toxicities—have had long-term benefits from just a single dose of these drugs. So, it may be that the 1 dose is good enough? That’s a unique problem, that could come up here.
Jyoti D. Patel, MD: I think it’s interesting. Last week, I had 2 cases where patients had been treated in the community with durvalumab after chemoradiation. Both of these patients had pretty significant pneumonitis, which was closer to the radiation. And so, again, we sort of had 2 competing causes. Both patients came to me, I think, because the oncologists who they were seeing were feeling guilty about holding the durvalumab. Because of these profound progression-free survival gains, they were interested to see if I’d say, “It’s OK. You’ve probably had enough. Let’s take a little break and continue the steroids.”
Mark Kris, MD: I think it’s important to remind folks that concurrent chemoradiation, given in the best way, is a tough regimen.
Walter J. Curran Jr., MD: Absolutely.
Mark Kris, MD: Looking at that Nasser Hanna, MD, trial, with a sort of real-world statewide or beyond regimen, I believe that a third of the people were hospitalized due to various adverse effects —fevers, pneumonitis—in those who received concurrent chemoradiation alone. So, it’s a tough regimen. But in my mind, it is very justified because of the goal. If we can cure more people—now, hopefully, with the addition of durvalumab—it’s worth pushing the envelope.
Transcript Edited for Clarity