ALK抑制剂在治疗NSCLC脑转移中的疗效及安全性研究进展

Research Progress in the Efficacy and Safety of ALK Inhibitors in the Treatment of NSCLC Brain Metastasis

肺癌是全球死亡率最高的恶性肿瘤之一,其中非小细胞肺癌(non-small cell lung cancer,NSCLC)占所有肺癌病理类型的80%-85%。NSCLC中有30%-55%的患者发生脑转移。据估计,5%-6%的脑转移患者存在间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合。ALK融合阳性NSCLC患者在接受ALK抑制剂后获得了非常显著的疗效。经过十余年的迅速发展,ALK抑制剂已经形成三代同堂的局面:即第一代——克唑替尼(Crizotinib);第二代——阿来替尼(Alectinib)、布格替尼(Brigatinib)、塞瑞替尼(Ceritinib)、恩沙替尼(Ensartinib);第三代——洛拉替尼(Lorlatinib)。这些药物在ALK融合阳性NSCLC脑转移患者中显示出不同的疗效。由于此类药物众多,ALK抑制剂的选择给临床医生带来了困扰。因此,本文旨在对ALK抑制剂在NSCLC脑转移中的治疗效果和安全性进行综述,以期为临床医生提供治疗选择的依据。

Lung cancer is one of the most lethal malignancies in the world,with non-small cell lung cancer(NSCLC)accounting for approximately 80%-85%of all pathological types.Approximately 30%-55%of NSCLC patients develop brain metastases.It has been reported that 5%-6%of patients with brain metastases harbor anaplastic lymphoma kinase(ALK)fu-sion.ALK-positive NSCLC patients have shown significant therapeutic benefits after treatment with ALK inhibitors.Over the past decade,ALK inhibitors have rapidly evolved and now exist in three generations:first-generation drugs such as Crizotinib;second-generation drugs including Alectinib,Brigatinib,Ceritinib,and Ensartinib;and third-generation drugs like Lorlatinib.These drugs have exhibited varying efficacy in treating brain metastases in ALK-positive NSCLC patients.However,the numer-ous options available for ALK inhibition present a challenge for clinical decision-making.Therefore,this review aims to provide clinical guidance by summarizing the efficacy and safety of ALK inhibitors in treating NSCLC brain metastases.