David Carbone, MD, PhD: Dr Dietrich, what do you have to consider when you are considering adding immunotherapy to both surgical patients and radiation patients?

Martin Dietrich, MD, PhD: I think it’s important that we have 2 fantastic options for local control: both surgery and radiation. In my opinion, radiation is probably a little bit underutilized for early-stage disease. I think many small tumors are probably very well controlled with radiation alone, but who do we identify [as] at risk of systemic involvement? I think what we have to acknowledge is that a lot of the lessons we’ve learned from metastatic disease are now replicating into earlier disease. Biomarkers matter, even though we have a lot of approvals that may be biomarker agnostic, we do have to think about a patient with an ALK fusion or an EGFR mutation differently than [one with] a KRAS or a RET fusion. Other mutations may be playing a role. I think that’s one of the challenges. I’m not sure that we need to repeat a lot of these lessons. I think we’ll see that immunotherapy in early-stage disease in a [patient with an EGFR mutation] is going to be equally ineffective. I think our data would suggest that, like it is in the metastatic setting. [Meeting] the challenge of having timely, in a curative intensity, timely molecular testing, does make it even more important. These are the tumor-specific factors that I’m talking about, [for which] we really have to have broad molecular profiling on these patients. I do think there is a prognostic hint that circulating tumor DNA is a more metastatic phenotype, but oftentimes they’re false negatives. Deciding early on that this has to be done enables us to actually start reflex testing on all stages; that I agree with you. The recurrence rates for stage I disease are, in any other tumor space, unacceptably high and an acute indication for systemic therapy. Those are the tumor factors that are basically opening up the options that a patient has. Then we have to match it, obviously, to the individual patient’s performance status, patient preferences, and kind of a shared decision-making process. But what we’ve learned in metastatic disease we cannot forget in early-stage disease, probably even more impactful when I look at data for ADAURA for adjuvant osimertinib in the post-EGFR setting or now with neoadjuvant immunotherapy. That data has amplified and impacted, in my observation of the data. Obviously, we don’t have comparisons, early versus late introduction of these therapies, in many cases, but we first have to decide what’s biologically reasonable and then what’s clinically feasible in a second step.

David Carbone, MD, PhD: But in addition to tumor factors, there are patient factors that guide whether immunotherapy is appropriate. Obviously, if you have a heart-lung transplant, it’s probably not a good patient for immunotherapy, but more subtle things like a history of rheumatoid arthritis or Crohn disease as a teenager that’s been quiescent later on in life. What other host factors do you use to help guide whether immunotherapy is appropriate or not?

Martin Dietrich, MD, PhD: It’s a difficult question. In clinical trials, we typically have somewhere between 2 to 5 years of exclusion. I have to say [that] in my practice, we’ve [become] very accepting of the risk of escalating autoimmune [adverse] effects. It’s very difficult to transplant patients. Unfortunately, in lung cancer, that’s not a very big problem. We see this more in the skin cancer space. But for patients with rheumatoid arthritis or patients with a history of Crohn disease or plaque psoriasis, oftentimes we have to accept that the principal problem in their health history has shifted to lung cancer.

David Carbone, MD, PhD: Lung cancer is bad for you too.

Martin Dietrich, MD, PhD: I have very few patients where, by definition, we exclude immunotherapy as an option. I think we’re going to push that limit. I think our supportive therapies have gotten better and better. Our steroid-sparing properties have gotten better. I can’t say that I really have a predictive pattern of how patients are responding. Some patients have aggravation, some patients don’t. In my opinion, in a life-or-death setting of lung cancer, many of these problems become relative. I can translate what the clinical trial did into my reality that about 20% of my patients have autoimmune predisposition, and I don’t think it’s reasonable to exclude these patients.

David Carbone, MD, PhD: We’ve actually hired a rheumatologist into our medical oncology division who sits in the clinic with us and helps us manage all of these new anticytokine autoantibodies that they have available that they didn’t have 5 years ago. They’re very skilled at managing those things. That’s very helpful. That’s another angle to multidisciplinary care for patients that we discussed previously.

Transcript is AI-generated and reviewed by AJMC editorial staff.