Drs Lee and Saxena on the Study of PD-L1 Expression in EGFR-Mutated NSCLC

“We see a lot of different patients with EGFR-mutated disease [who] have different PD-L1 expression levels. Does this say something about the biology of the tumor? Can this be used as a predictive or prognostic biomarker in the frontline setting when patients are being treated with first-line osimertinib?”

Jonathan Wennan Lee, MD, MSc, chief hematology/oncology fellow in the Weill Department of Medicine at NewYork Presbyterian-Weill Cornell Medicine; and Ashish Saxena, MD, PhD, an associate professor of clinical medicine at Weill Cornell Medical College and an assistant attending physician at NewYork-Presbyterian Hospital, discuss the rationale for examining PD-L1 expression as a biomarker of response in patients with EGFR-mutant non–small cell lung cancer (NSCLC).

Lee noted that this disease is composed of various mutation types with distinct biological profiles. Lee observed that as the paradigm of therapeutic options continues to expand, there is a critical unmet need for prognostic and predictive biomarkers to assist oncologists in navigating treatment selection. Lee pointed out that this clinical challenge led to the investigation of the role of PD-L1 expression levels in EGFR-mutant NSCLC, as PD-L1 is a marker that is already widely tested for across the globe.

Lee raised the fundamental question of what varying PD-L1 levels signify regarding the underlying biology of the tumor. In a retrospective study, Lee and colleagues sought to determine whether PD-L1 expression could function as a reliable predictive or prognostic biomarker in the frontline setting for patients receiving first-line osimertinib (Tagrisso). Saxena added that this investigation was informed by preclinical findings, which revealed a complex interplay between the PD-L1 and EGFR surface receptors. Saxena noted that these receptors operate in close proximity to one another, indicating that their relationship is more integrated than previously recognized.

The experts highlighted that this investigation represents a shift in the traditional research focus. They explained that whereas many studies investigate how EGFR mutations influence the success of immunotherapy, this work examines how the binding of antibodies to PD-L1 directly affects EGFR-mutated lung cancers.