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ASCO 2026 | irAE severity & clinical outcomes with ICI therapy in NSCLC: Lung MAP analysis
Diane Tseng, MD, PhD, Fred Hutch Cancer Center, Seattle, WA, discusses the relationship between immune-related adverse event (irAE) severity and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs), using data from Lung MAP sub-studies. In ICI-naive patients, low-grade irAEs were associated with more favorable OS compared to both absent and high-grade irAEs, an association not observed in the ICI-exposed cohort. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
So we asked the question, what is the relationship between the severity of immune adverse events and clinical outcomes of non-small cell lung cancer patients treated with checkpoint immunotherapy? This question has never previously been asked in the context of a multi-institutional study where squamous cell non-small cell lung cancer patients were well represented and where patients received checkpoint immunotherapy in the absence of chemotherapy...
So we asked the question, what is the relationship between the severity of immune adverse events and clinical outcomes of non-small cell lung cancer patients treated with checkpoint immunotherapy? This question has never previously been asked in the context of a multi-institutional study where squamous cell non-small cell lung cancer patients were well represented and where patients received checkpoint immunotherapy in the absence of chemotherapy. We hypothesized that the patients experiencing mild immune adverse events would have improved clinical outcomes compared to patients who did not experience immune adverse events and patients who experienced severe immune adverse events. We performed an analysis looking at the relationship between the maximum severity of immune adverse events and overall survival. And we performed a landmark analysis at 6, 12, and 24 weeks, as well as Cox modeling. One unique feature of our analysis is we performed separate analyses of patients who were immunotherapy naive and patients who were immune checkpoint inhibitor refractory. Our cohort of patients included over 400 patients treated on the lung map, sub-studies S1400A, I, and 1800A. These patients received PD-1 checkpoint immunotherapy with or without CTLA-4 checkpoint immunotherapy in the context of second-line and beyond disease. We discovered that the patients who were immunotherapy naive, that patients experiencing mild immune adverse events, defined as grade 1 to 2, had improved overall survival outcomes compared to patients who did not develop immune adverse events and patients who developed severe immune adverse events. Interestingly, we did not observe those associations in patients who were previously exposed to immune checkpoint inhibitor therapies, and that likely reflects that that’s a select patient population and that patients who previously experienced severe immune adverse events were excluded from those subsequent studies. We’re currently performing analysis looking at clinical and genomic features that could potentially be associated with immune adverse event severity.
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