Ly Ashley C, Olin Jacqueline L, Smith Morgan B
Wingate University School of Pharmacy, Wingate, NC.
Wingate University School of Pharmacy, Wingate, NC
Am J Health Syst Pharm. 2018 Apr 15;75(8):515-522. doi: 10.2146/ajhp170266. Epub 2018 Feb 21.
The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosage and administration, and place in therapy of alectinib for treatment of patients with non-small-cell lung cancer (NSCLC) are reviewed.
In patients with NSCLC driven by mutations of , the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC. Alectinib is a next-generation ALK inhibitor initially approved by the Food and Drug Administration for use in patients with metastatic -positive NSCLC who are intolerant of or have disease progression during crizotinib therapy. In clinical trials, alectinib was found effective for delaying disease progression and, more importantly, reducing brain metastases in patients with NSCLC who developed resistance or intolerance to previous crizotinib therapy. Published data from clinical trials indicate that the most common grade 1 and 2 adverse effects associated with alectinib use are fatigue, constipation, peripheral edema, and myalgia; the most common grade 3 or 4 reactions include increases in creatine phosphokinase, alanine aminotransferase, and aspartate aminotransferase levels.
Alectinib appears to be effective and safe for use in patients with metastatic -positive NSCLC, with demonstrated superiority over crizotinib in terms of PFS rates. Research to better define ALK inhibitor resistance mechanisms and alectinib's place in therapy is ongoing.
综述阿来替尼治疗非小细胞肺癌（NSCLC）患者的药理学、药代动力学、临床疗效、安全性和耐受性、剂量与用法以及在治疗中的地位。
在由间变性淋巴瘤激酶（ALK）编码基因发生突变驱动的NSCLC患者中，已发现使用ALK抑制剂克唑替尼治疗的中位无进展生存期（PFS）为10.9个月；然而，使用克唑替尼常见治疗失败和肿瘤进展至脑转移，这促使开展研究以寻找更有效且耐受性更好的靶向NSCLC主要致癌驱动因素的ALK抑制剂。阿来替尼是一种新一代ALK抑制剂，最初被美国食品药品监督管理局批准用于对克唑替尼治疗不耐受或出现疾病进展的转移性ALK阳性NSCLC患者。在临床试验中，发现阿来替尼可有效延缓疾病进展，更重要的是，可减少对先前克唑替尼治疗产生耐药或不耐受的NSCLC患者的脑转移。临床试验发表的数据表明，与使用阿来替尼相关的最常见1级和2级不良反应为疲劳、便秘、外周水肿和肌痛；最常见的3级或4级反应包括肌酸磷酸激酶、丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平升高。
阿来替尼用于转移性ALK阳性NSCLC患者似乎有效且安全，在PFS率方面显示出优于克唑替尼。关于更好地确定ALK抑制剂耐药机制以及阿来替尼在治疗中的地位的研究正在进行中。
