ASCO 2025 | Identifying cause of disparities in NSCLC outcomes

We had a panel session yesterday just talking about modern knowledge about leptomeningeal disease. We used a specific lung cancer patient as the index case for the discussion. It was somebody who had lung cancer with one of the classical EGFR mutations who presented with leptomeningeal disease. The panel was a multidisciplinary panel. There was a neuro-oncologist, there was myself, a thoracic medical oncologist, there was another oncologist from the Netherlands, and then there was a radiation oncologist. And what we essentially did was talk about how do you identify patients who have leptomeningeal disease. One of the key points we raised was that the incidence of brain metastasis and leptomeningeal metastasis specifically is much higher in patients with EGFR-mutated lung cancers than other types of lung cancers. It’s at least twice the level. So it’s important for people to remember that and to pay attention to patient symptoms and to look for this. We talked about how you identify leptomeningeal disease, both on imaging studies, which we recommended needed to be both a brain MRI and an MRI of the spine. We talked about the radiologic findings that should show you, raise concern about that. We talked about the need for testing the spinal fluid, not just for cytology, which is, while very specific, not very sensitive. And we talked about newer methods of identifying leptomeningeal disease in the spinal fluid. So circulating tumor cells, circulating tumor DNA are emerging much more sensitive ways of identifying. And then we talked about treatment. So for this specific scenario, EGFR mutated lung cancer. We spoke about the prevailing evidence for treatment selection. We referred to the FLAURA2 trial, which used a combination of osimertinib, a third-generation tyrosine kinase inhibitor that blocks EGFR and combined with chemotherapy as the preferred treatment because in that trial FLAURA2 patients who had CNS metastases were the one subset that seemed to particularly benefit from adding chemotherapy. We debated the level of evidence to support doubling the dose of the targeted agent. I think we agreed that the level of evidence was really, really weak. Even though people tend to do that, there’s no real justification for doing that. We talked about the role of radiation therapy, especially proton beam radiation therapy, which was what this index patient received. And then we also talked about how to monitor patients for response and recurrence, including these newer cutting-edge diagnostics, circulating tumor cells, circulating tumor DNA. So that was the discussion yesterday.

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