Drs Lee and Saxena on the Role of PD-L1 as a Biomarker of Osimertinib Response in EGFR-Mutated NSCLC

“Having [higher levels of] PD-L1 [expression] makes [patients with EGFR-mutated NSCLC] less responsive to single-agent TKIs, specifically 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 findings from a retrospective study evaluating the role of PD-L1 expression as a predictive biomarker of response for patients receiving first-line osimertinib (Tagrisso) monotherapy for the treatment of EGFR-mutated non–small cell lung cancer (NSCLC).

Lee observed that identifying molecular signatures is a critical step in determining which patients are likely to benefit most from single-agent TKIs. Lee highlighted that the study demonstrated a clinical trend in which patients with tumors harboring higher levels of PD-L1 expression had less favorable outcomes. By separating the study population into PD-L1–negative and PD-L1–positive disease cohorts, the investigators found that patients with PD-L1–positive disease experienced a lower response rate (odds ratio, 0.29; 95% CI, 0.08-0.92, P = .046), as well as shorter progression-free survival (HR, 1.49; 95% CI, 0.87-2.56; P = .10) and overall survival (HR, 1.53; 95% CI, 0.89-2.62; P = 0.12) durations. Lee noted that although these results did not reach the threshold for statistical significance, the study may have been underpowered to definitively answer the question but still revealed a biological trend.

Saxena pointed out that these findings are consistent with those of other contemporary studies, which collectively indicate that elevated PD-L1 levels may be prognostic for worse outcomes when using first-line targeted therapies. Saxena noted that these data fit into a broader scheme of understanding osimertinib resistance in NSCLC. Saxena concluded that larger, more robust studies are necessary to confirm these observations and to fully elucidate why increased PD-L1 expression appears to render tumors less responsive to single-agent TKIs.