Exon-level TP53 alterations and PD-L1 expression identified by pretreatment NGS stratify survival in EGFR-mutant non-small cell lung cancer treated with first-line osimertinib
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Osimertinib is the standard first-line treatment for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) sensitizing mutations. However, the response duration varies among patients, meaning predictive biomarkers are needed. Therefore, this study explores the role of co-occurring genomic alterations in predicting survival outcomes. Methods: Clinical data were extracted from electronic medical records. We retrospectively analyzed next-generation sequencing (NGS) data for EGFR-mutant NSCLC patients treated with first-line osimertinib treatment. Results: Among the patients who underwent first-line osimertinib treatment, baseline NGS data were analyzed from treatment-naïve tissue for 48 patients. Alterations in TP53 were the most common co-mutation event (62.5%). Patients with mutations in TP53 exon 5, which encodes a critical region in the DNA-binding domain, exhibited a reduced treatment period [hazard ratio (HR) =7.67; 95% confidence interval (CI): 1.77–33.32; P=0.007] and overall survival (OS) (HR =9.29; 95% CI: 2.06–41.86; P=0.004) compared to EGFR-mutant NSCLC patients possessing the wild-type TP53. In particular, co-expression of programmed death-ligand 1 (PD-L1) with TP53 exon 5 mutation showed worse time to treatment discontinuation (TTD) (HR =9.27; 95% CI: 1.42–60.34; P=0.02) and OS (HR =14.54; 95% CI: 2.03–104.32; P=0.008). Conclusions: Mutations in TP53 exon 5 are associated with a shorter first-line osimertinib treatment duration and OS. These findings might provide insight into a combination strategy for the first-line treatment of EGFR mutant NSCLC patients or a patient selection strategy for adjuvant osimertinib.
Institutions: Asan Medical Center, University of Ulsan
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7117566518
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