Department of Surgery, Medical University of Vienna , Vienna , Austria.
Respiratory Oncology Unit, Otto Wagner Hospital , Vienna , Austria.
Expert Opin Pharmacother. 2019 Sep;20(13):1551-1561. doi: 10.1080/14656566.2019.1643839. Epub 2019 Jul 22.
: Brigatinib is a second-line inhibitor for the treatment of rearranged anaplastic lymphoma kinase (ALK) in lung cancer patients which has significant activity against brain metastases. This tyrosine kinase inhibitor (TKI) overcomes a wide range of ALK mutations which confer therapeutic resistance and is increasingly applied in first-line therapy due to improved benefit for patients compared to crizotinib, the current standard of care. : The authors review the development and characteristics of brigatinib and discuss the optimal clinical use and sequence of the application of ALK inhibitors in patients progressing under therapy. : ALK-rearranged NSCLC can be treated with a broad range of approved and novel inhibitors at various stages of therapy, including the second-line therapeutic brigatinib. Besides this TKI, the second-line ALK inhibitors alectinib and ceritinib, as well as the third-line lorlatinib are approved for the treatment of ALK-positive NSCLC patients. The main challenge is to find sequences and combinations of ALK inhibitors which provide the best benefit for the patients.
布加替尼是一种针对肺癌患者中重排间变性淋巴瘤激酶（ALK）的二线抑制剂，对脑转移具有显著疗效。这种酪氨酸激酶抑制剂（TKI）克服了广泛的ALK 突变，这些突变赋予了治疗耐药性，并且由于与目前的标准治疗药物克唑替尼相比，为患者带来了更好的益处，因此越来越多地应用于一线治疗。作者回顾了布加替尼的发展和特点，并讨论了在治疗进展中ALK 抑制剂的最佳临床应用和应用顺序。ALK 重排非小细胞肺癌（NSCLC）可以在治疗的各个阶段使用广泛的批准的和新型的抑制剂进行治疗，包括二线治疗的布加替尼。除了这种 TKI 外，二线 ALK 抑制剂阿来替尼和塞瑞替尼，以及三线 lorlatinib 也被批准用于治疗 ALK 阳性 NSCLC 患者。主要的挑战是找到能为患者提供最佳获益的 ALK 抑制剂的序列和组合。
