Neoadjuvant Chemo Plus Immunotherapy in Resectable NSCLC

Neoadjuvant Chemo Plus Immunotherapy in Resectable NSCLC

June 15, 2022 0 By Jennifer Walker

At the recent American Society of Clinical Oncology (ASCO) annual meeting, updated data were presented on the CheckMate 816 trial, a phase III study looking at the efficacy and safety of adding the immune checkpoint inhibitor nivolumab (Opdivo) to neoadjuvant chemotherapy in patients with operable lung cancer.

In this first of four exclusive episodes, MedPage Today brought together three leaders in the field — moderator Roy S. Herbst, MD, PhD, of Yale Cancer Center in New Haven, Connecticut, is joined by Jorge Nieva, MD, of the Keck School of Medicine of USC in Los Angeles, and Sarah Goldberg, MD, also of Yale Cancer Center — for a roundtable discussion on the emerging data on neoadjuvant therapy in the setting of non-small cell lung cancer and how it is changing how patients with early-stage disease are treated.

Following is a transcript of their remarks:

Herbst: Welcome to our roundtable on lung cancer here in Chicago at ASCO 2022. I’m Dr. Roy Herbst from the Yale Cancer Center. I’m also joined by my colleague, Dr. Sarah Goldberg from the Yale Cancer Center, and Dr. Jorge Nieva from the University of Southern California. We’re here today to discuss new things that are happening, exciting new things, in lung cancer. So why don’t we start with the first question: How are you enjoying Chicago so far — good meeting?

Nieva: It’s been a great meeting, Roy. Really happy that I can be with you today. I think we’ve had some great presentations, there’ve been obviously great things happening at the plenary sessions, but I think the lung cancer sessions have been exciting as well.

Herbst: Right. Would you agree, Sarah?

Goldberg: I agree. It’s been great to be back in person in Chicago and see all the great presentations.

Herbst: Okay. So let’s take a few topics and really dig down. The first is neoadjuvant therapy. So of course at the AACR [American Association for Cancer Research] meeting, we heard about the 816 trial, Checkmate 816 neoadjuvant therapy. We’ve had some updates here. What’s the impact of that, Sarah, on the treatment of lung cancer?

Goldberg: Yeah, so I think that the 816 trial, which is the combination of chemotherapy and nivolumab, is neoadjuvant therapy for non-small cell lung cancer prior to resection. I think that was incredibly impactful.

I think we had seen before then that neoadjuvant immune therapy has a really impressive, I think, pathologic response. And so now with the combination of chemotherapy with immune therapy, that pathologic response looks even higher than with chemo alone. And we’re seeing good surgical outcomes, and I think really again, when we look at patient outcomes, disease-free survival benefit there as well.

And so I think that has been a game changer and has been great to see the emerging data from that trial. So I think that really has changed how we think about treating patients with early-stage cancer.

Herbst: What do you think, Jorge? You’ve got my old friend Tony Kim with you — are you using this now in clinical practice?

Nieva: Well, you know, we were a big enrolling site for IMpower30. And so that really was a clinical trial that we enrolled quite a few patients to. And so we’ve been doing the neoadjuvant paradigm with immunotherapy for a while.

For patients who are not enrolling in a clinical trial, I think CheckMate 816 is a great option for them as well. What I’m really excited about is the fact that it takes very little immunotherapy to get the benefit for the patients. I mean, we’re just talking about three doses, and they didn’t continue it after the operation, suggesting that we can really achieve benefits with immunotherapy with relatively short durations of exposure.

Herbst: Right. You mentioned IMpower, that means that’s a different drug. So this is an atezolizumab study, similar study?

Nieva: Yeah. So IMpower 30 was a study we had at USC where we used atezolizumab in the neoadjuvant setting prior to surgery. And unlike the CheckMate study, though, it gave additional atezolizumab after the operation.

So I think we’re going to be left with a number of options for our patients moving forward, because, of course, many of the different pharmaceutical companies are looking at extending their checkpoint inhibitors into the neoadjuvant space, as well as the adjuvant space.

And so I think we will have a lot of options for our patients to use it preoperatively, postoperatively, both. And we’re going to have to do a little bit more science and a little bit more work to figure out which one of those strategies is really going to be the best.

Herbst: I agree. And what do you think, Sarah? Assuming there’s no trial, what are the barriers to doing this? I would assume you need to discuss this at tumor board. We had one this morning, I don’t know if you joined it today.

Goldberg: I did. I did actually, it was actually 6:30 am in this time zone.

Herbst: I didn’t, but many of us, we all have sites where we have, we’re four or five deep in all the different specialties, at least. How does this work around the country to get someone keyed up for this?

Goldberg: It actually came up today in tumor board, because this is a very quickly evolving area. And so we’ve heard about some of the trials we’ve just been talking about. So now we have been thinking about neoadjuvant chemotherapy plus immune therapy. There’s also the adjuvant atezolizumab data, where that also has an improvement in disease-free survival. And so if patients don’t get neoadjuvant therapy and they go for surgery, adjuvant atezolizumab is an option.

And then specifically for our stage III patients — can’t forget that a lot of them are unresectable and so they might get chemoradiation, and then we’re giving them durvalumab. So I think the stage III space is almost the most complicated in some ways, because a lot of these patients that we previously said, well, maybe surgery’s not appropriate, maybe now with some neoadjuvant chemoimmune therapy followed by surgery, that might be an appropriate strategy.

So we’re having a lot of discussions in tumor board about maybe we should be broadening our considerations of who we might think about taking for surgery. The previous stage III patients that we might have said, well chemoradiation is most appropriate — can we think about a surgical strategy for this patient with neoadjuvant therapy instead of chemoradiation and immune therapy.

Herbst: Right, with all the players in the room to discuss it.

Goldberg: Yeah, exactly. And I think that that’s what’s going to be so important is really before anyone gets any treatment, before they go for surgery, before they get their neoadjuvant, anything — sitting down with radiation oncology, surgery, medical oncology, and really trying to understand what the options are, what’s on the table and what might make the most sense.

And actually, maybe I’ll mention one other thing, which is the biomarkers. So biomarkers are still really important. We need to understand what the PD-L1 is. And then we also have to look at EGFR upfront as well. We haven’t talked about that. We’re only talking about immune therapy. But understanding what the EGFR mutation status is before surgery is actually really important, because if someone has an EGFR mutation, that might be someone where you want to think about adjuvant osimertinib, as opposed to this neoadjuvant or adjuvant immune therapy strategy.

So that’s going to be important to know upfront as well now.

Herbst: Right. So you agree, Jorge? Communication alignment, what’s your take on this?

Nieva: Oh, absolutely. You know, the big concern of the surgeons, of course, is going to be, is the patient going to get to surgery if they get neoadjuvant therapy? And we saw in CheckMate 816 that about a quarter of the patients didn’t.

From the medical oncology perspective, we’re wondering, well, if the patient has surgery first, will they make it to adjuvant therapy? Because really, we want to make sure that our patients get as much therapy as possible. And we’ve seen in many of the adjuvant studies that relatively few patients make it all the way through the course of therapy, and just over half are able to do that.

So I think we need to find better ways of making sure that our patients benefit from all the modalities, because I think the more modalities we use on our patients, chemotherapy, as well as surgery, the better outcomes we have.

Of course, what’s the right role of radiation? I think we had a very nice discussion yesterday in one of the sessions about, maybe there will be some new strategies to begin to incorporate radiation with some of these lower-dose, sort of immune-sensitizing ways of using stereotactic radiation.

Goldberg: And actually I’ll just make a comment about radiation since you brought it up. I think one thing sometimes we had considered in some patients with stage III disease previously was chemoradiation followed by surgery. And I think that that probably is now not really part of our option list.

I think with neoadjuvant chemo plus immunotherapy, I think that is probably going to be more where we’re thinking in a neoadjuvant strategy. I don’t think chemoradiation followed by surgery is going to be an option for our patients really anymore.

Herbst: I agree. There’s some toxicity associated with that.

Goldberg: That as well.

Herbst: Especially big procedures.

Well, my take on this is, you know, immunotherapy works. And bring it to the earliest stages of disease, where it will work more. And we’re seeing that. We still have to work out some of the particulars, but we’re seeing that here in ASCO. Neoadjuvant approaches, adjuvant approaches, and now we’re fine-tuning the biomarkers.

So really, really good news for patients. It gives us a lot more to offer.

Nieva: Absolutely.

Herbst: Great. Thanks.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams. Follow