Efficacy and Safety of Third-Generation EGFR-TKIs Combined with Radiotherapy for Advanced NSCLC with Typical EGFR Mutations: A Retrospective Study

Abstract

Objective

To evaluate the efficacy and safety of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in combination with radiotherapy (RT) for patients with advanced non-small cell lung cancer (NSCLC) harboring typical EGFR mutations.

Methods

Patients who received treatment with third-generation EGFR-TKIs alone or in combination with RT were retrospectively enrolled at a single center. The primary endpoint was progression-free survival (PFS). Differences in PFS between the two groups were assessed via the Kaplan-Meier method. Additionally, a subgroup analysis was conducted to further explore the effect of thoracic RT combined with EGFR-TKIs.

Results

This study included a total of 260 patients, among whom 81 patients received third-generation EGFR-TKIs and 179 patients received third-generation EGFR-TKIs plus RT. There was a significant difference in median PFS (mPFS) (13.0 versus18.1 months, P= 0.0003) between the two groups. Moreover, third-generation EGFR-TKIs plus thoracic RT significantly improved the mPFS (13.0 versus23.7 months, P< 0.0001). We observed that third-generation EGFR-TKIs plus RT increased the incidence of pneumonia, but all the cases were grade 1 or 2.

Conclusion

The addition of RT can delay the occurrence of acquired resistance to third-generation EGFR-TKIs, thereby

significantly prolonging PFS in advanced NSCLC patients. RT for primary lung lesions exhibited a significant synergistic effect with EGFR-TKI treatment, and the adverse events of the combination therapy were acceptable.

Keywords

Non-small cell lung cancer / Epidermal growth factor receptor / Tyrosine kinase inhibitors / Radiotherapy

© The Author(s), under exclusive licence to Huazhong University of Science and Technology 2025

Supplementary Information The online version contains supplemen- tary material available at https://doi.org/10.1007/s11596-025-00032-4.

Acknowledgements Not applicable.

Author Contributions Wen-xuan Zhang contributed to methodology, investigation, data curation and writing-original draft; Hui-chan Xue contributed to methodology and data curation. Ye Zhao and Shuang- bing Xu contributed to conceptualization, supervision, project admin- istration and writing-review &editing. All authors reviewed the manuscript.

Data Availability The data are available from the corresponding author on reasonable request.

Declarations

Conflict of interest The authors have declared that no competing interest exists.

Consent for Publication Not applicable.

Human Ethics This study was approved by the Institutional Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Ethics Approval and Consent to Participate All procedures performed in studies involving human participants comply with the ethical standards of the Declaration of Helsinki. This study was approved by the Institutional Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. As this study was retrospective, the Institutional Ethics Committee waived the requirement of obtaining the informed consent.

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