NSCLC: Discussing Molecular Biomarkers and Treatment Decisions with Patients


Meghan J. Mooradian, MD, shares her approach to communicating with patients with NSCLC regarding treatment decisions based on molecular biomarkers.


Martin Dietrich, MD, PhD: How do you relay the impact of these multimutational analyses you’re using for therapy selection, as an expert who is probably seeing patients from all over the world? Additionally, when you are advising on these regimens—many are not familiar with these combination immunotherapies—how do you approach that discussion?

Meghan J. Mooradian, MD: From a patient-centered language scenario, I try to instill the therapies that we have and the data we are armed with, and why their molecular subtype may or may not be the right lock and key. I try to distill it down to how can we best get their immune system to respond. With these STK11/KEAP1 tumors that we think do have alternations in the tumor microenvironment, maybe the metabolic state of the tumor, and are kind of “immunologically cold,” we find that the standard of the PD-1 therapy alone, which they may or may not have seen on TV commercials, with or without chemotherapy, may not be enough in terms of jump starting it. We’ve talked a bit already about CTLA-4, but I think with CTLA-4’s unique ability to prime T cells, assist T-cell tumor infiltration, and lead to a more diverse T-cell response, we can frame it into, how can we try to personalize the treatment the best we possibly can for you based on all of the molecular data we have?

I try to put it into framing tumor-specific characteristics and patient-specific characteristics when we’re trying to find the optimal treatment for the person in front of us. I think we all do that, taking into account histologic data, that PD-L1 TPS [tumor proportion score], and molecular signature. Then obviously factors about the patients themselves and their past medical history are important. Do they have an autoimmune condition? Do they require immunosuppression? Would that obviously make us a bit more reticent to feel enthusiastic about immunotherapy? What are their priorities and their goals of care? I think we encompass all of that when we meet a patient in the clinic.

Then we try to guide them to the best of our ability on why one therapy will hopefully be the optimal therapy for them. With the notion too that, as you pointed out previously, what we’re really hoping for is improving the durability of response. In that, when we’re looking back at some of the data from the CheckMate 227 and CheckMate 9LA trials, which we’re having 3-year updates, we are seeing that tail on the curve rise. Even for those challenging patient populations, those squamous cells, the patients with PD-L1 tumors, and now these patients with these difficult molecular subtypes. I do think we can inform patients in this complex landscape. We just have to do so thoughtfully. Then you just march forward together. But it’s an exciting time to be a thoracic oncologist. It is challenging. There are a lot of data to integrate when we’re thinking through what’s going to be the best path forward for the patient in front of us.

Martin Dietrich, MD, PhD: That was an excellent summary of personalized immunotherapy. I think we’ve gotten pretty good about matching our targeted therapies. With immunotherapy, I think we still have a lot to learn.

Transcript edited for clarity.

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