Zhou Qing, Lu Shun, Li Yong, Jia Fujun, Li Guanjun, Hong Zhen, Lu You, Fan Yun, Zhou Jianying, Liu Zhe, Li Juan, Wu Yi-Long
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
Zhongguo Fei Ai Za Zhi. 2022 Aug 20;25(8):555-566. doi: 10.3779/j.issn.1009-3419.2022.101.39.
Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy. .
间变性淋巴瘤激酶（ALK）融合是非小细胞肺癌（NSCLC）中第二常见的致癌驱动突变。作为新一代第三代ALK酪氨酸激酶抑制剂（TKI），劳拉替尼已显示出强大的效力，并且在克唑替尼和第二代ALK TKI治疗期间检测到的ALK结构域内的多种耐药突变谱方面具有脑渗透临床活性。劳拉替尼通常耐受性良好，但有独特的药物不良反应/不良事件，包括高脂血症和中枢神经系统影响，这些大多为轻度至中度严重程度，可通过调整剂量和/或标准医疗干预来控制。对于ALK阳性的晚期NSCLC患者，应评估其基线特征和既往用药情况，告知其潜在毒性，并定期监测以平衡获益和风险。此外，多学科专家小组对于制定全面的诊断和治疗策略至关重要。
