Application of Lazertinib in Brain Metastases of Non-Small Cell Lung Cancer

Abstract

Lazertinib is an oral, brain-penetrating, irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor that selectively targets EGFR T790M resistance mutations and common activation mutations (Ex19del, L858R), while exhibiting weaker inhibitory effects on wild-type EGFR. It provides a novel therapeutic option for brain metastases in EGFR-mutated non-small cell lung cancer. This article systematically reviews the pharmacological characteristics, preclinical studies, clinical evidence, safety profile, and resistance mechanisms of lazertinib. Preclinical studies demonstrated that lazertinib exhibits significant intracranial distribution advantage and antitumor activity in brain metastasis mouse models, with higher tumor exposure levels in the brain compared to plasma and superior efficacy over control drugs. In clinical trials, whether as first-line or second-line treatment, lazertinib monotherapy showed a high objective remission rate in intracranial tumors, and brought lasting benefits to patients with brain metastasis, and a clear effect was also observed in patients with meningeal metastasis. In the combination therapy, lazertinib combined with amivantamab can further improve the prognosis of patients with brain metastasis and significantly prolong the progression-free survival time in the brain. In terms of safety, the adverse reactions of lazertinib monotherapy are mainly mild to moderate, and the adverse reactions of combined therapy are generally controllable. Venous thromboembolism can be effectively managed by preventive anticoagulation. The mechanism of drug resistance mainly includes EGFR C797S mutation and MET amplification. In a word, Lazertinib showed significant and lasting intracranial anti-tumor activity in patients with brain metastases from EGFR mutation NSCLC, which provided a new effective treatment choice for this high-risk group.