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Central nervous system efficacy of third generation vs. first generation EGFR-TKIs in the first line treatment for EGFR-mutated non-small cell lung cancer with central nervous system metastases: a phase 3 randomized controlled trials based meta-analysis

   
@article{JTD125613,
	author = {Jiongli Gan and Shaofeng Zhu and Yan Fang and Jiaqiang Wang and Tiande Liu and Jing Cai},
	title = {Central nervous system efficacy of third generation vs. first generation EGFR-TKIs in the first line treatment for EGFR-mutated non-small cell lung cancer with central nervous system metastases: a phase 3 randomized controlled trials based meta-analysis},
	journal = {Journal of Thoracic Disease},
	volume = {0},
	number = {0},
	year = {2026},
	keywords = {},
	abstract = {Background: Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastases poses significant treatment challenges, as first-generation EGFR-tyrosine kinase inhibitors (TKIs) (FGET) show limited CNS efficacy. Although third-generation EGFR-TKIs (TGET) exhibit superior CNS penetration, the optimal choice for first-line treatment remains debated. This meta-analysis aims to resolve this controversy by directly comparing the CNS efficacy of TGET vs. FGET in patients with EGFR-mutant NSCLC and CNS metastases.Methods: A thorough literature search was performed for phase 3 randomized controlled trials (RCTs) comparing TGET and FGET in patients with EGFR-mutated NSCLC and CNS metastases. The primary outcome was CNS-progression-free survival (PFS), and secondary outcomes included overall survival (OS), PFS, CNS response rates, and adverse events (AEs). The study was registered in PROSPERO (ID: CRD42024629581).Results: A total of 5 phase 3 RCTs (AENEAS, FLAURA, FURLONG, IBIO-103, and LASER301) met the inclusion criteria. TGET demonstrated superior efficacy in CNS-PFS [hazard ratio (HR): 0.44 (0.33, 0.58), P},
	issn = {2077-6624},	url = {https://jtd.amegroups.org/article/view/125613}
}