Abstract—Lung cancer is one of the malignant tumors with the highest morbidity and mortality rates in the world, of which Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 80%-85%. Epidermal Growth Factor Receptor (EGFR) mutations are prevalent in Asian NSCLC patients, and such patients are more prone to brain metastases. With the iterative development of EGFR-Tyrosine Kinase Inhibitors (EGFR-TKIs), significant progress has been made in therapeutic strategies for brain metastases from EGFR mutation-positive NSCLC. This paper systematically reviews the research advances in targeted therapy in this field. Based on the mechanism of impact, the intracranial activity and clinical application of the first-to fourth-generation EGFR-TKIs are elaborated in detail, and the R&D trends of the third-generation drugs and their resistance-related fourth-generation drugs are analyzed. The combination of targeted drugs with chemotherapy, radiotherapy, antiangiogenic therapy and other targeted drugs is also discussed in this paper. Furthermore, the paper presents the breakthrough of a new generation of high blood-brain barrier penetrating drugs. Finally, this paper proposes the prospects of transforming lung cancer brain metastases from terminal events to chronic diseases that can be managed for a long time by optimizing full-course management strategies.
 
Keywords—non-small cell lung cancer, EGFR mutations, brain metastases, targeted therapy, EGFR-tyrosine kinase inhibitors, combination therapy, blood-brain barrier, drug resistance mechanism

Cite: Jingxuan Pang and Lewei Li, "Advances in Targeted Therapy for EGFR-mutated NSCLC Brain Metastasis," International Journal of Pharma Medicine and Biological Sciences, Vol. 15, No. 3, pp. 97-106, 2026.

Copyright © 2026 by the authors. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).