Objective This study aimed to investigate the prognostic factors for the treatment efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with EGFR exon 21 L858R mutation.
Methods The study enrolled patients with advanced EGFR L858R-mutant NSCLC who received first-line EGFR-TKI treatment between January 2019 and April 2024. Cox regression analyses were performed to identify the prognostic factors from clinical characteristics and concomitant genetic alterations that influenced progression-free survival (PFS) and overall survival (OS).
Results According to the study of a cohort of 120 patients, we found that more metastatic organs (≥3 organs), specific metastatic patterns (liver and bone involvement), concurrent TP53 mutations, and worse Eastern Cooperative Oncology Group Performance Status (ECOG PS) were associated with shorter PFS. And ECOG PS was an independent predictive factor for PFS. Similarly, metastatic organs ≥ 3 (HR, 2.719; 95 % CI, 1.386-5.333; p = 0.004), ECOG PS of 2 (HR, 10.756; 95 % CI, 4.002-28.906; p < 0.001), and body mass index (BMI)>24 kg/m2 (HR, 0.335; 95 % CI, 0.147-0.760; p = 0.009) were associated with worse OS. We also observed that patients harboring TP53 co-mutations demonstrated significantly inferior PFS compared with their TP53 wild-type counterparts (13.7 months vs. 18.8 months; p = 0.006).
Conclusions This study identified several factors significantly associated with worse response to EGFR-TKIs in NSCLC patients with EGFR L858R mutation and respective independent predictive factors for PFS and OS. These findings could enable personalized therapeutic efficacy assessment to facilitate clinical decision-making for EGFR L858R-mutant NSCLC patients treated with EGFR-TKIs.
Ethics statement
This study was approved by the Peking University Third Hospital medical science research ethics committee (Ethics Approval Number: M2023746).
CRediT authorship contribution statement
Yan’e Liu: data curation, data analysis, writing and editing manuscript. Lu Chen: data curation, data analysis, writing and editing manuscript. Xin Zhu: writing and editing manuscript. Hua Zhang: statistical analysis, editing manuscript. Baoshan Cao: conceptualization, reviewing and editing manuscript, funding acquisition.
Conflict of Interest Statement
The authors confirm that there are no conflicts of interest.
Acknowledgments
This study was supported by the National Key R&D Program of China (2020AAA0105203).
Appendix A. Supplementary material
Supplementary data associated with this article can be found in the online version at doi:10.1016/j.gmg.2025.100051.
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