Lung Cancer Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Yonsei Med J. 2022 Sep;63(9):799-805. doi: 10.3349/ymj.2022.63.9.799.
Lazertinib is an oral, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that forms an irreversible covalent bond to the Cys797 residue in the ATP-binding site of the EGFR kinase domain and exhibits a high selectivity for sensitizing and T790M EGFR mutations. In January 2021, it was first approved for the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) patients with EGFR T790M who had previously received EGFR TKI therapy based on LASER201, a phase I/II trial. At a recommended dose of 240 mg, lazertinib achieved an encouraging anti-tumor activity in both extra- and intracranial lesions. With a high half-maximal inhibitory concentration for EGFR wildtype tumors, it is anticipated to pose a lower risk of skin and cardiac adverse events compared to osimertinib. Lazertinib is currently being investigated as a monotherapy in first-line treatment and in combination with amivantamab under various settings. In this review, we systematically summarize the preclinical and clinical data of lazertinib and discuss future perspectives on the treatment of EGFR-mutant NSCLC.
拉泽替尼是一种口服、不可逆的第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI），它与 EGFR 激酶结构域的 ATP 结合位点中的 Cys797 残基形成不可逆的共价键，对敏感和 T790M EGFR 突变具有高度选择性。2021 年 1 月，基于 LASER201 的一项 I/II 期临床试验，拉泽替尼首次被批准用于治疗先前接受过 EGFR TKI 治疗的 EGFR T790M 阳性的晚期或转移性非小细胞肺癌（NSCLC）患者。在推荐剂量为 240mg 时，拉泽替尼在颅外和颅内病变中均表现出令人鼓舞的抗肿瘤活性。由于对 EGFR 野生型肿瘤的半最大抑制浓度较高，与奥希替尼相比，预计其皮肤和心脏不良事件的风险较低。拉泽替尼目前正在各种情况下作为单药一线治疗和与 amivantamab 联合进行研究。在这篇综述中，我们系统地总结了拉泽替尼的临床前和临床数据，并讨论了其治疗 EGFR 突变型 NSCLC 的未来前景。
