阿美替尼治疗非小细胞肺癌的研究进展

肺癌是全球癌症相关死亡的最常见原因,其中85%为非小细胞肺癌(non-small-cell lung cancer,NSCLC),表皮生长因子受体(epidermal growth factor receptor,EGFR)是治疗晚期NSCLC最重要的靶点之一。第一、二代EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitor,EGFR-TKI)一直是晚期EGFR突变NSCLC患者的标准治疗方法,但获得性耐药几乎不可避免,主要耐药原因为T790M突变。阿美替尼是中国首个自主研发的第三代EGFR-TKI,对包括L858R和19号外显子缺失在内的EGFR敏感突变,以及T790M耐药突变均具有活性,同时保留野生型EGFR,克服了第一、二代EGFR-TKI的耐药性和选择性问题,其临床前和临床研究均显示出良好的有效性与安全性,为我国NSCLC患者提供了新的用药选择。本综述对阿美替尼的结构、作用机制、临床前研究、药动学,在NSCLC治疗中的临床疗效、安全性,以及与其他第三代EGFR-TKI的比较进行了总结,为该药的临床使用及未来的探索研究提供参考。

Research progress in aumolertinib in the treatment of non-small-cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide, of which non-small-cell lung cancer (NSCLC) accounts for 85%. The epidermal growth factor receptor (EGFR) is one of the most important targets in the treatment of advanced NSCLC. First- and second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKI) remain the standard of care for patients with EGFR-mutated advanced NSCLC, but acquired drug resistance is almost inevitable. The main resistance mechanism is T790M mutation. Aumolertinib is the first self-developed third-generation EGFR-TKI in China, which is active against EGFR-sensitive mutations including L858R and exon 19 deletion, as well as T790M-resistant mutations while sparing the wild-type EGFR. Aumolertinib successfully overcomes the resistance and selectivity problems of first- and second-generation EGFR-TKIs. The safety and efficacy of aumolertinib were confirmed by clinical trials, providing a new drug option for NSCLC patients in China. This review summarized the structure and mechanism of action, preclinical studies, pharmacokinetics, and clinical efficacy of aumolertinib in the treatment of NSCLC, so as to provide reference for clinical use and future exploration of aumolertinib.