Dr Cameron on the Prognostic Value of PD-L1 for Outcomes With Osimertinib in EGFR+ NSCLC

"Some oncologists will just outright ignore PD-L1 expression when it comes to EGFR-mutated [NSCLC], and [this study indicates that] maybe we need to take a closer look at that."

Robert Cameron, MD, PhD, a Hematology/Oncology fellow at the University of Chicago, discussed findings from a single-center, retrospective study evaluating the prognostic relevance of PD-L1 expression in patients with EGFR-mutated non–small cell lung cancer (NSCLC) who received first-line treatment with osimertinib (Tagrisso). The data were presented as part of the OncLive Fellows Forum on Thoracic Oncology, which took place during the 2025 ASCO Annual Meeting.

The study explored whether PD-L1 expression, which has known predictive value in EGFR wild-type NSCLC, may also have prognostic or therapeutic implications in EGFR-mutant disease. Investigators observed a trend toward shorter progression-free survival (PFS) and lower response rates among patients with high PD-L1 expression compared with those with low PD-L1 expression. However, these differences did not reach statistical significance,likely due to the limited sample size. Despite the lack of statistical power, Cameron noted that the findings align with prior reports and raise the possibility that PD-L1 status may have underappreciated clinical relevance in this subset of patients.

Importantly, Cameron emphasized that these findings challenge the prevailing practice of disregarding PD-L1 status in the management of EGFR-mutated NSCLC. He suggested that higher PD-L1 expression might eventually inform risk stratification or therapeutic escalation, such as consideration of osimertinib plus chemotherapy or alternate combinations, though these hypotheses remain untested.

The study also found an apparent association between high PD-L1 expression and concurrent TP53 mutations, a genomic alteration commonly linked to poor outcomes across NSCLC subtypes. Whether this co-occurrence reflects a biologically relevant interaction, a shared driver of aggressive disease, or an incidental association remains unclear. Cameron highlighted the need for further investigation into the potential interplay between PD-L1 expression and TP53 mutations and their combined impact on treatment outcomes with targeted therapy.

Overall, these results underscore the complexity of biomarker interpretation in EGFR-mutant NSCLC and suggest a possible role for PD-L1 expression in refining prognostication or guiding future trial designs.