Yang Mingyi, Luo Weichi, Zhou Qing
School of Medicine South China University of Technology, Guangzhou 510080, China.
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Southern Medical University, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Zhongguo Fei Ai Za Zhi. 2023 Apr 20;26(4):281-290. doi: 10.3779/j.issn.1009-3419.2023.101.12.
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase and its rearrangements occur in non-small cell lung cancer (NSCLC), resulting in signal dysregulation in kinase domain. As a new generation of potent ALK tyrosine kinase inhibitors (TKIs), Brigatinib was approved in China in March 2022 as a treatment for locally advanced or metastatic NSCLC patients with ALK rearrangement positive. Brigatinib significantly improved the survival, cranial efficacy and quality of life compared to Crizotinib in clinical trials. Brigatinib is generally well tolerated. Brigatinib has been one of the preferred treatments and an addition of options in ALK-rearranged NSCLC. Pulmonary toxicity is one of the adverse effects observed during the treatment of TKIs and deserves the intense attention of clinicians, despite of its low incidence rate. Pulmonary toxicity reported during the treatment of Brigatinib has shown distinct clinical presentations, such as early-onset (median time to onset, 2 days) and rapid tolerance and reversibility of symptoms. In view of this, the concept of early-onset pulmonary events (EOPEs) was proposed and established during the submission for regulatory review and approval. We focused on clinical characteristics, potential mechanism of etiology, and management strategies of EOPEs to provide clinicians evidence for better clinical decision support. .
间变性淋巴瘤激酶（ALK）是一种受体酪氨酸激酶，其重排在非小细胞肺癌（NSCLC）中发生，导致激酶结构域信号失调。作为新一代强效ALK酪氨酸激酶抑制剂（TKIs），布加替尼于2022年3月在中国获批，用于治疗ALK重排阳性的局部晚期或转移性NSCLC患者。在临床试验中，与克唑替尼相比，布加替尼显著提高了生存率、颅内疗效和生活质量。布加替尼总体耐受性良好。布加替尼一直是ALK重排NSCLC的首选治疗方法之一和新增选择。尽管肺部毒性发生率较低，但它是TKIs治疗期间观察到的不良反应之一，值得临床医生密切关注。布加替尼治疗期间报告的肺部毒性表现出不同的临床症状，如早发（中位发病时间为2天）以及症状的快速耐受性和可逆性。鉴于此，在提交监管审查和批准期间提出并确立了早发性肺部事件（EOPEs）的概念。我们关注EOPEs的临床特征、潜在病因机制和管理策略，为临床医生提供更好的临床决策支持依据。
