David Carbone, MD, PhD: Dr Dietrich, do you think it’s fair to say that, given the fact that it hasn’t been formally tested, but [with] the cross-trial comparisons that we do have, do you think it’s fair to say that chemoimmunotherapy before surgery is better than operating on a patient and giving chemoimmunotherapy after surgery?

Martin Dietrich, MD, PhD: Well, I think there are 2 factors. One is the biology of T cell and tumor cell interactions happening intratumorally, so it makes little sense to remove the tumor microenvironment as this priming field for treatment. There is an underlying biological rationale, and then the data would support it. If I think about this, not only neoadjuvant versus adjuvant, but the extension of it into metastatic disease, then metastatic disease with poor performance status will be seen as an impression. It is that the earlier we treat, the better the patient is nourished, the better the patient is in performance status, the better the immune system can function. Immunotherapy is not a way of treating cancer. It’s a way of activating the immune system to really do its job, to fight cancer. Looking at the underlying engine of the patient here makes me think that the earlier we introduce immunotherapy, the better the respective outcomes are. Obviously, [it is] limited by their nonmodifiable factors like PD-L1 and mutational status and then other factors. In my opinion, the earlier, the better. I think we will shift, like we did in breast [cancer], like we did in rectal cancer. We will shift [to] an approach that will, eventually…and we’ve seen this in a very nice head-to-head comparison in melanoma, leaning on data of neoadjuvant outcompeting adjuvant immunotherapy with a hazard ratio of 0.5. It makes complete sense to me, and the data would support it.

I do have to say, in criticism of our neoadjuvant data, the standard of care for stage III disease is chemoradiation followed by immunotherapy, not neoadjuvant chemotherapy. But even with this criticism, the stand-alone impact that chemoimmunotherapy up front had, I think this is the standard of care for resectable disease. It’s obviously a loaded term, and it’s also a term that I define a little bit differently than a surgeon would. For me, resectability is determined after neoadjuvant chemoimmunotherapy; I think there should be a confirmatory step. I have raised my expectations for outcomes. I want to see fewer pneumonectomies, fewer bilobar resections. There’s hope that this is really going to change the shift. But in my opinion, the standard of care for at least stage II, but certainly many stage Ib disease in consideration, is neoadjuvant chemoimmunotherapy, and for me, it’s the [CheckMate] 816 regimen. At this point, I’m not sure what additional benefit longer therapies will provide, but the earlier, the better. Then intact tumor microenvironment with no antibiotics, no steroids, and no other confounding factors, when the immune system is the strongest, is the way to go for the data that we have right now.

David Carbone, MD, PhD: I think I would agree with you, and the concern that I hear voiced is, well, if you give neoadjuvant therapy, some patients may not get their surgery, and that might harm the patient because maybe it grew a little bit and became inoperable in that 3 cycles of chemotherapy.

Martin Dietrich, MD, PhD: But that’s not really what the data would suggest. The data would really give us reassurance that the surgical outcomes, if anything, moved in the right direction.

David Carbone, MD, PhD: If you are going in to operate on a stage, especially N2-positive stage III, there’s a fraction of those surgeries that don’t happen even if you go right in and do them. Those patients who get a few cycles of chemoimmunotherapy, and then the surgeon says it gets in there, for example, and can’t do it, I personally don’t think that they’re harmed if you follow that with definitive chemoradiation. In fact, there are some early hints that giving chemoimmunotherapy before chemoradiation may actually be better than doing it after, or at least it’s not worse. I don’t think you’re harming these patients by doing that.

Transcript is AI generated and reviewed by an AJMC editor.