Shah Dhairavi, Shah Dhaara, Ndandji Suzy, Kar Supratik
Chemometrics and Molecular Modeling Laboratory, Department of Chemistry and Physics, Kean University, Union, NJ, USA.
Expert Opin Drug Metab Toxicol. 2025 Jul;21(7):789-800. doi: 10.1080/17425255.2025.2507404. Epub 2025 May 21.
Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, accounting for 85% of cases worldwide. Despite advancements in treatment, many patients are diagnosed at advanced stages, and resistance to therapy, such as EGFR inhibitors, remains a significant challenge. Lazertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) developed by Yuhan Corporation and Janssen Biotech, targets EGFR mutations, including T790M, which confer resistance to earlier-generation TKIs.
This review explores lazertinib's development, mechanism of action, clinical efficacy, and safety profile. Preclinical studies demonstrated its superior selectivity for mutant EGFR and blood-brain barrier penetration compared to osimertinib. Clinical trials highlight its efficacy as monotherapy and in combination with amivantamab, showing improved progression-free survival and response duration in patients with advanced NSCLC.
Lazertinib represents a promising advance in the treatment of EGFR-mutated NSCLC, particularly for patients with brain metastases or resistance to previous EGFR TKIs. However, emerging resistance mutations, such as C797S, underscore the need for continued innovation, including combination therapies and fourth-generation TKIs. Future research must address these challenges to optimize treatment outcomes for NSCLC patients.
非小细胞肺癌(NSCLC)是最常见的肺癌形式,占全球病例的85%。尽管治疗取得了进展,但许多患者在晚期才被诊断出来,并且对治疗的耐药性,如对EGFR抑制剂的耐药性,仍然是一个重大挑战。来泽替尼是由韩国柳韩洋行(Yuhan Corporation)和杨森生物技术公司(Janssen Biotech)开发的第三代表皮生长因子受体酪氨酸激酶抑制剂(EGFR TKI),靶向EGFR突变,包括对早期TKI产生耐药性的T790M突变。
本综述探讨了来泽替尼的研发、作用机制、临床疗效和安全性。临床前研究表明,与奥希替尼相比,它对突变型EGFR具有更高的选择性,并且能够穿透血脑屏障。临床试验突出了其作为单药治疗以及与阿米万他单抗联合使用的疗效,显示晚期NSCLC患者的无进展生存期和缓解持续时间有所改善。
来泽替尼是EGFR突变型NSCLC治疗方面的一项有前景的进展,特别是对于有脑转移或对先前EGFR TKI耐药的患者。然而,新出现的耐药突变,如C797S,凸显了持续创新的必要性,包括联合疗法和第四代TKI。未来的研究必须应对这些挑战,以优化NSCLC患者的治疗效果。