Perioperative Approaches to Lung Cancer

Derick Alison
Derick Alison
12 Min Read

MedPage Today brought together three expert leaders for a virtual roundtable discussion on lung cancer: Moderator Roy Herbst, MD, PhD, is joined by Anne Chiang, MD, PhD, and So Yeon Kim, MD, all from the Yale Cancer Center in New Haven, Connecticut.

This second of four exclusive episodes focuses on the best treatment approaches for patients with non-small cell lung cancer in the perioperative setting.

You can see other videos in this series here.

Following is a transcript of their remarks:

Herbst: Hi, I am Dr. Roy Herbst from the Yale Cancer Center where I’m the deputy director and the assistant dean for translational research. I’m thrilled to be joined by some of my colleagues today on this MedPage Today program where we’re going to talk about some very exciting and new topics in non-small cell and small cell lung cancer. I’m joined by Dr. Anne Chiang and Dr. So Yeon Kim.

OK, let’s pick another topic. Let’s talk about the perioperative space. That tumor board that we all sort of rub our eyes at early morning and get together every Monday here at Yale and we see patients and we look at x-rays and tissue. What’s happening there? I guess you’ve got to make a decision after diagnosis on whether the patients going to be surgical or not in their treatment and whether they should get neoadjuvant treatment. And there are all these trials now. We have three, four, we’re about to hear about the perioperative trials for nivolumab [Opdivo]. What do you think, Anne? What do we do in someone for neoadjuvant therapy right now? What’s our drug of choice?

Chiang: That’s a loaded question. I think that this really is an embarrassment of riches or approaches and the most important thing about early-stage disease is to have a multidisciplinary discussion. So as you talked about, tumor board is increasingly more attended and increasingly more exciting, and maybe sometimes fractious. But I think it’s really important to have discussions, look at the films together, talk about the patients. We have, for example, the CheckMate 816, that’s the neoadjuvant trial of three cycles of chemo plus IO [immunotherapy] versus chemo alone, and then surgery. In that trial, the pathologic complete response was 25% for nivo [nivolumab]-chemo versus about 4% for chemo alone.

And I think that’s really important because that is something that was completely new to the lung cancer field — that we could actually achieve pathologic complete responses in a quarter of the patients. Now in that trial, there are patients that don’t make it to surgery, and I think that’s something that we hear about from our surgeons. They’re worried that the patients, if they don’t make it to surgery, they’re not going to get definitive treatment.

I think also for our adjuvant therapies, the IMpower010 and our KEYNOTE trial that shows that adjuvant atezo [atezolizumab (Tecentriq)] in PD-L1-positive patients or adjuvant pembro [pembrolizumab (Keytruda)] definitely shows a benefit. Thinking about which is the better approach, we don’t have an answer, but I know that as a SWOG member of the lung committee, I know that we’re working on that.

And together within the cooperative group setting, there’s going to be basically a pragmatic trial that says perioperative versus adjuvant approaches — you pick. And then we’ll try and keep an eye on what happens to the patients and figure out what is the best approach for our patients.

Herbst: Sounds wonderful, Anne. So Yeon, what’s your experience with neoadjuvant? I guess the drug that we would use now would be nivolumab and CheckMate 816, that’s all that’s approved at the time of this filming, but there are many other things percolating right now. What’s your sense? Have you had a good experience with it? When someone has a complete response or a partial response, what do you do? What do you do after?

Kim: Yeah, so that’s a great question. Yes. So [nivolumab based on results from] CheckMate 816 is the only neoadjuvant therapy that’s currently FDA approved, although there are trials that have looked at perioperative therapies that have demonstrated, I would say, pretty similar [pathologic] CR [complete response] rates and major pathologic response rates [MPRs]. So the question is, there’s several questions.

I think number one, what do we do after patients who’ve received neoadjuvant therapy? And then number two, should we choose neoadjuvant versus perioperative therapies? And until we have a side-by-side comparison of the two, it’ll be very difficult to choose between the two treatments.

Now going back to your question, Dr. Herbst, about what do we do after neoadjuvant chemo-IO? So there’s variabilities in provider treatment decisions for patients who’ve achieved [pathologic] CR or at least major pathologic response, it’s been demonstrated that they do very well as far as their event-free survival, almost encroaching 90%.

So in patients who’ve received a very good response — so viable tumor less than 10% — I think I would probably go for surveillance, since there are toxicities that we cannot ignore with additional immunotherapies as well. For patients who’ve possibly had a response, but maybe not MPR or pathologic complete response, I would think about additional immunotherapy. And for those who did not achieve a response at all, for example, let’s say that they had 90% to 95% viable tumor, I’m not really certain if they’re going to actually respond to additional immunotherapy because they’ve never really responded initially.

So, that, we would consider talking to the patient about potentially additional therapies, although there’s really no trial to support that yet. So it’ll have to be a patient and a physician shared decision-making process.

Herbst: Great. Thanks, So Yeon. Now, Anne, when do we make that decision? So the adjuvant, so who still gets adjuvant anymore? So you’re sitting there, and my sense is that not everyone can go to neoadjuvant. We have to be careful, as you said, in our decisions. But driver mutation patients, are they still going in the adjuvant route? I guess, how do we decide when someone’s going to get the ADAURA type regimen? Are they already sequenced before we see them in the tumor board? And then I guess the ALINA trial with ALK [inhibitors] coming down the pike, what’re your thoughts in this area?

Chiang: I think that the more information that we have upfront is going to be helpful to the patient and to making decisions. So I do think that doing reflex testing on biopsies and utilizing liquid biopsies are very important, so that we can make those decisions upfront. Because it’s very clear that if you’re PD-L1-positive or if you have an EGFR mutation, that you should have a different path. So I think that’s really important to tease out beforehand.

I do think that there may be some patients, and certainly in our tumor boards, the patients that we’re thinking about upfront surgery are our patients with EGFR mutations or patients who have very, very early-stage tumors — that may change. I think that it’s really hard to beat the ADAURA results that have translated now to overall survival benefits, as you’ve talked about many times, Roy, and … some of the other driver mutations are behind. ALK is next. And I think I’m really excited to hear about the ALINA trial and that I think will be practice-changing for our patients.

Chemo, is that something that we’re going to use anymore in the future or, according to the FLAURA2 trial, are we going to start to use chemo with EGFR-directed or biomarker-directed therapy? All of those are yet to find out.

Herbst: Thanks, Anne. So Yeon, your experience with adjuvant TKI [tyrosine kinase inhibitors] and your prediction for, will we do this with RET and with KRAS? May I ask?

Kim: So I think the positive press release on the ALINA trial speaks to both the group of the patients with ALK mutations, but also speaks to the other targeted patients as well. So with RET, ROS, NTRK, they’re usually typically a very rare subpopulation of patients. So with two trials that demonstrate benefit of adjuvant therapy, I think that supports physicians in making more parallel decision making as far as possibly considering, for example, for a ROS1 patient, adjuvant entrectinib [Rozlytrek].

Of course, we’ll have to potentially discuss with insurance about that as well until we have a trial, but we might never have a trial with those rare subsets of patients. So I think the two positive trials really support for potentially also adjuvant therapy for the less common targetable mutations.

Herbst: OK, my take, you know, it’s an exciting time. We have to be even more conversant with our surgical colleagues. We haven’t even talked about radiation. Let’s not forget the PACIFIC trials and chemoradiation. Some patients maybe shouldn’t go to surgery — let’s not forget that. For those who are going to surgery, there’re going to be three or four choices to pick from and we’re going to have to figure this all out. Dare I say, we might have to all do a pre-competitive type of collaboration. We need to look at all this data and samples and molecular studies. The pragmatic trial that we heard about from Anne that might be happening in the cooperative groups might help us to pull it all together.

But really, really good for patients. And we always knew we could cure lung cancer in the earliest diseases. Now we’re bringing together the newest targeted and immunotherapies, really quite exciting. So, thank you both.

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