Dr Lee on Research Collaborations Studying PD-L1 as a Biomarker in NSCLC

“We are starting to see consistent results with poorer outcomes associated with higher levels of PD-L1 expression, and the driving question is: Why?”

Jonathan Wennan Lee, MD, MSc, chief hematology/oncology fellow in the Weill Department of Medicine at NewYork Presbyterian-Weill Cornell Medicine, discussed the emerging clinical significance of PD-L1 expression as a potential biomarker of first-line osimertinib (Tagrisso) resistance in EGFR-mutated non–small cell lung cancer (NSCLC).

Lee and colleagues performed a retrospective analysis of the potential predictive and prognostic value of PD-L1 expression in patients with EGFR-mutated NSCLC receiving osimertinib in the first-line setting. Lee observed that multiple research groups, including a group from Australia investigating approximately 300 patients, have demonstrated consistent results linking higher levels of PD-L1 expression with poorer clinical outcomes. Although PD-L1 is traditionally viewed through the lens of immune evasion as a resistance mechanism, Lee noted that the key question centers around the underlying biological mechanism behind this correlation. Current investigations are exploring how high PD-L1–expressing tumors differ intrinsically from non-expressing tumors, with hypothesis-generating ideas indicating that factors such as MET overexpression may reflect fundamental biological differences in the disease, he explained.

To address these mechanistic gaps, Lee highlighted an ongoing international collaboration led by researchers at Cornell. This partnership involves both basic science and translational researchers who are interested in identifying novel biological drivers of resistance, he said. Lee emphasized the importance of this work in the context of a rapidly evolving clinical paradigm for EGFR-mutated disease, noting the necessity for data to remain informative and helpful for guiding real-world treatment decisions. The project is designed to be iterative, with initial findings expected to generate further inquiries that will be validated through laboratory testing, according to Lee. Ultimately, the goal is to define whether PD-L1 serves as a surrogate for a specific biological phenotype that necessitates distinct therapeutic strategies for patients with PD-L1–high NSCLC.