Impact of PD-L1 on first-line osimertinib outcomes in EGFR-mutant NSCLC: Real-world data from the AURORA25 study and meta-analysis
Abstract
Introduction: The prognostic significance of PD-L1 expression in EGFR-mutant non-small cell lung cancer (NSCLC) treated with first-line osimertinib remains uncertain. This study evaluated its association with survival in a real-world cohort, supported by meta-analysis. Materials: Retrospective multicentre study using AURORA cohort (ACTRN12625000038493). Primary endpoint was real-world progression-free survival (rwPFS) comparing PD-L1 high (≥50 %) vs low (0–49 %). Secondary endpoints included overall survival (OS), osimertinib duration and response, and analyses at ≥1 %/≥25 %/75 % cut-points. Kaplan-Meier and Cox models were applied. Meta-analysis of studies to 18April2025 reporting first-line osimertinib outcomes by PD-L1 expression was performed. Results: Among 216 patients from 15 centres, median rwPFS was 24.8 months (95 %CI 19.7–29.6). Higher PD-L1 (≥25 %, ≥50 %, ≥75 % versus below each threshold) was associated with shorter rwPFS. The adjusted HR for PD-L1 ≥50 % (n = 35/216, 16 %) vs 0–49 % (n = 181, 84 %) was 3.03 (95 %CI 1.85–4.96, p < 0.001). Median OS was 56.9 months (95 %CI 23.3–57.4): 40.4 with PD-L1 ≥50 and 57.0 with 0–49 %. PD-L1 correlated with shorter OS in unadjusted analyses, with ≥75 % remaining significant after adjustment (HR 2.09, 95 %CI 1.01–4.33, p = 0.046). Meta-analysis of six studies confirmed shorter rwPFS (HR 2.32, 95 %CI 1.16–4.64, p = 0.0178) and OS (HR 2.38, 95 %CI 1.16–4.86, p = 0.0176) for PD-L1 ≥50 % vs 0–49 %. Conclusions: PD-L1 ≥50 % was associated with over twofold risk of progression or death in EGFR-mutant NSCLC on first-line osimertinib. Supported by meta-analysis, results suggest PD-L1 expression is a negative prognostic factor, and these patients may benefit from intensified first-line strategies with prospective evaluation.
Document Type
Journal Article
Date of Publication
1-1-2026
Volume
211
PubMed ID
41371099
Publication Title
Lung Cancer
Publisher
Elsevier
School
School of Medical and Health Sciences
Copyright
subscription content
Comments
Alexander, M., Itchins, M., Felthun, J., Nagrial, A., Brown, L. J., O’Byrne, K., Mersiades, A. J., Hughes, B. G., Warburton, L., Kong, B. Y., Moore, M., Blinman, P., Bowyer, S., Clay, T., Spelman, T., Pavlakis, N., Solomon, B. J., & Kao, S. (2025). Impact of PD-L1 on first-line osimertinib outcomes in EGFR-mutant NSCLC: Real-world data from the AURORA25 study and meta-analysis. Lung Cancer, 211, 108854. https://doi.org/10.1016/j.lungcan.2025.108854