Mark A. Socinski, MD: This is a population that, historically, even though we don’t cure the majority of them, we kind of approach them in a curative way. Heather, I wanted to get your thoughts on the discussion you have, in the point you try to make to the patient about chemoradiotherapy being curative, and that sort of thing?

Heather A. Wakelee, MD: This is really a key point. Even though we don’t cure the majority, we do definitely cure some patients. And how that’s framed is really important. One of the key things I always try to do when I’m talking to a bigger audience, and to the patient…because many of them have been told before, “This is stage III disease. There’s nothing else that can be done. Here’s some chemotherapy.” There’s still a lot of nihilism out there, even if we’ve had these amazing advances in what we’re able to do to help our patients.

So I talk with the patients about the fact that we are trying to cure the disease. Inevitably, the question of surgery comes up. And even if the patient hasn’t brought it up, we’ll talk about why we’re considering that patient wouldn’t be a surgical candidate—assuming that’s a patient with IIIb or IIIa disease.

We have a multidisciplinary tumor board, as I’m sure you all do. We meet every week. And our standard is that any patient with stage III disease is discussed there. The images are in front of radiation oncologists as well as surgeons and the medical oncologist so we can all talk together to figure out what we think, upfront, is the best approach.

Back in the day, the big question was, when and should surgery ever be brought in? And for some of those approaches, we had the chemoradiation upfront and then we would stop and go to surgery. There was a risk that you would not be giving a definitive radiation course, and that break would be so long that then you had to split the course, which wasn’t ideal. I think we’ve moved away from that. We really do try to make sure, upfront, we’ve decided that this is a patient going to surgery, in which case they’re not going to have radiation upfront. Our group currently just isn’t a big fan of that. I think that’s a whole other topic for conversation.

Mark A. Socinski, MD: It’s a whole other program.

Heather A. Wakelee, MD: A whole other program. But our plan is that if they’re going to surgery, we will consider doing upfront chemotherapy, neoadjuvant chemotherapy, and perhaps on trial with immune therapy. That’s a different question. But if they’re not going to, then it’s a definitive chemoradiation. Depending on how long the timing is going to be, we often will give 1 cycle of chemotherapy during the planning for the radiation, because that’s going to take a week or 2. And we’ll get into talking about PACIFIC later, but I think for some patients getting that extra cycle in can be potentially helpful if it’s not going to delay the definitive of start of radiation. So I’ll talk with the patients about it. It’s a long course. It can be a rough 6 weeks. But our hope is to cure the patient. We do have a lot of patients with EGFR mutations, ALK translocations, which we often do identify upfront. And again, I think testing at that stage is a little bit controversial.

Mark A. Socinski, MD: That’s the next question I’m going to ask Paul, coming up.

Heather A. Wakelee, MD: So even in that setting, we talk about the definitive chemoradiation.

Mark A. Socinski, MD: So Paul, now that Heather brought it up, obviously molecular testing, broad-based testing in PD-L1 [programmed death-ligand 1] is an integral part of managing stage IV disease, right? We don’t quite know what to do with all of that in stage III disease, although, to your point, it’s often done. So you often know the information. What do you think should be done? And if stuff is done, does that cloud your judgment, or does that change your judgment?

Paul K. Paik, MD: I think there are probably a couple of different ways to answer that. From the most rigorous data-driven perspective, there really is no defined role for doing molecular testing insofar, as we have no….

Mark A. Socinski, MD: In stage III?

Paul K. Paik, MD: In stage III disease, insofar, as we have no guidance on the use of these targeted therapies in that context. PD-L1 testing, we’ll talk about a little bit later, when it comes to the PACIFIC trial and some recent unplanned analyses when it comes to PD-L1—negative patients. So that, I do find, is useful to have. I think the other way to answer this is from a practical perspective. We know, as we discussed before, that a subset of these patients will have occult metastatic disease, if we repeat PET [positron emission tomography] imaging in a relatively short period. So these are patients who we will need this information on. And so, ordering it upfront makes a lot of sense because then we don’t have to wait for the results to come back.

And in addition to that, I think unfortunately, still a fair number of these patients will develop recurrent disease, or frankly, metastatic disease, where we’ll need this information. Just having it on hand without, again, having to wait or rebiopsy offers a lot of power, in terms of discussing and assuaging patients when that situation arises.

Mark A. Socinski, MD: But would we all agree that with the diagnosis of an oncogenic driver in stage III disease, we don’t have any data to support targeted agents in that setting? Because this is a phone call I get twice a month, with a community oncologist who has tested and they have exon 19, and, “Shouldn’t I be giving them a TKI [tyrosine kinase inhibitor] versus chemotherapy in this setting?” Right?

Heather A. Wakelee, MD: There was a study completed in China that was presented at ESMO [European Society for Medical Oncology] last year. In patients who had stage III disease, they did look at giving an upfront EGFR TKI. And there’s certainly been attempts at trying to bring that in with the chemoradiation approach. Unfortunately, the big Cooperative Group study in the United States, which was identifying these patients upfront and giving them erlotinib, if they were EGFR mutated, or crizotinib, if they had an ALK in this sort of pre-chemotherapy radiation setting, failed to accrue and had to be closed. So we don’t really have an answer to that component.

So there are questions, but it does come up. And there are occasional patients who are quite frail or who really understand that this is not curative. It can be a bit nuanced. I practice in a place where half of my patients have EGFR mutations. So this comes up all the time. But yes, I completely agree with you that in a standard setting, if we have that information, it doesn’t change what we do right then with a definitive curative approach.

Mark A. Socinski, MD: Because for all we know, these patients actually might do better with chemoradiotherapy.

Heather A. Wakelee, MD: Might.

Mark A. Socinski, MD: There are some suggestive data on that, but it’s not clear.

Transcript Edited for Clarity