Impact of PD-L1 on first-line osimertinib outcomes in EGFR-mutant NSCLC: real-world data from the AURORA25 study and meta-analysis
- Author(s)
- Alexander, M; Itchins, M; Felthun, J; Nagrial, A; Brown, LJ; O'Byrne, K; Mersiades, AJ; Hughes, BGM; Warburton, L; Kong, BY; Moore, M; Blinman, P; Bowyer, S; Clay, T; Spelman, T; Pavlakis, N; Solomon, BJ; Kao, S;
- Journal Title
- Lung Cancer
- Publication Type
- Research article
- 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.
- Publisher
- Elsevier
- Keywords
- Humans; *Carcinoma, Non-Small-Cell Lung/drug; therapy/genetics/mortality/metabolism/pathology; *Lung Neoplasms/drug therapy/genetics/mortality/metabolism/pathology; *Acrylamides/therapeutic use; *Aniline Compounds/therapeutic use; ErbB Receptors/genetics; *Mutation; *B7-H1 Antigen/metabolism/genetics; Male; Female; Retrospective Studies; Middle Aged; Prognosis; Aged; Biomarkers, Tumor; Antineoplastic Agents/therapeutic use; Treatment Outcome; Indoles; Pyrimidines; Egfr; Meta-analysis; Nsclc; Osimertinib; Pd-l1; Real-world; Survival
- Department(s)
- Pharmacy
- Publisher's Version
- https://doi.org/10.1016/j.lungcan.2025.108854
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-01-13 02:21:05
Last Modified: 2026-01-13 02:23:51