脑转移在阴性非小细胞肺癌（NSCLC）中非常常见,尤其是在间变型淋巴瘤激酶（ALK）阳性的NSCLC中，累积发生率超过50％，与预后不良、症状负担高和生活质量下降有关。洛拉替尼是一种可穿越血脑屏障的第三代ALK酪氨酸激酶抑制剂（TKI），对早期代ALTK TKI的耐药突变具有很高的效力。2018年，基于1/2期研究结果，洛拉替尼在ALK阳性转移性NSCLC的二三线治疗中获得了加速批准。基于CROWN研究的中期分析结果显示，较善西罗替尼相比，洛拉替尼在ALK阳性转移性NSCLC病人的一线治疗中表现出更长的无进展生存期、颅内进展时间、反应持续时间和客观反应率，因此这一初始批准得到了扩展。本文是我们播客的文字记录，我们在其中讨论了控制脑转移发生的临床意义、选择一线治疗方案的考虑因素、脑转移患者和非脑转移患者观察到的疗效和安全性，以及在治疗中使用洛拉替尼的合理性和保留其作为后期治疗的理由。©2023. 作者。

Brain metastases are especially common in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), with a cumulative incidence of over 50% and associated with a poor prognosis, high symptom burden, and decreased quality of life. Lorlatinib is a brain-penetrant, third-generation ALK tyrosine kinase inhibitor (TKI), which has a high potency against resistance mutations seen with earlier generation ALK TKIs. In 2018, lorlatinib was granted accelerated approval in second- and third-line treatment for use in patients with ALK-positive metastatic NSCLC on the basis of phase 1/2 study results. This initial approval was expanded for first-line treatment of patients with ALK-positive metastatic NSCLC on the basis of the interim analysis of the phase 3 CROWN study showing longer progression-free survival, time to intracranial progression, duration of response, and objective response rate compared with crizotinib. This manuscript is a transcript of our podcast, in which we discuss the clinical significance of controlling the onset of brain metastases, considerations in selecting a first-line therapy option, efficacy and safety observed in patients with and without brain metastases, and rationales for using lorlatinib upfront versus reserving for a later line in therapy.© 2023. The Author(s).