Background: Central nervous system (CNS) metastases represent a significant source of morbidity and mortality for patients with ALK tyrosine kinase gene (ALK)‐positive NSCLC. Alectinib has demonstrated robust CNS activity in both crizotinib‐naive and crizotinib‐resistant settings. However, the CNS efficacy of alectinib has not been established in patients with untreated symptomatic, large CNS metastases. Methods: In this retrospective study, patients were eligible if they had advanced ALK‐positive NSCLC with large (defined as ≥1 cm) or symptomatic CNS metastases and received alectinib. Medical records and radiographic imaging were reviewed to determine treatment outcomes. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1. Results: Of the 19 patients, 15 (79%) had measurable CNS disease at baseline and were evaluable for response. The CNS objective response rate in these patients was 73.3% (95% confidence interval [CI]: 44.9%–92.2%), the CNS disease control rate was 100.0% (95% CI: 78.2%–100.0%), and the median CNS duration of response was 19.3 months (95% CI: 14.3 months–not evaluable). In 18 evaluable patients with measurable and/or nonmeasurable baseline CNS disease, the CNS objective response rate was 72.2% (95% CI: 46.5%–90.3%), the CNS disease control rate was 100.0% (95% CI: 81.5%–100.0%), and the median CNS duration of response was 17.1 months (95% CI: 14.3 months–not evaluable). All eight patients with symptoms attributable to CNS metastases had clinical improvement upon starting alectinib therapy. Six patients (32%) eventually required salvage brain radiotherapy. Conclusions: Alectinib demonstrated meaningful CNS efficacy in patients with ALK‐positive NSCLC with untreated symptomatic or large brain metastases.

中文翻译：

---

艾乐替尼在 ALK 阳性 NSCLC 和有症状或大的 CNS 转移患者中的疗效

背景：中枢神经系统 (CNS) 转移是 ALK 酪氨酸激酶基因 (ALK) 阳性 NSCLC 患者发病率和死亡率的重要来源。艾乐替尼在克唑替尼初治和克唑替尼耐药环境中均表现出强大的 CNS 活性。然而，尚未确定艾乐替尼对未经治疗的有症状的大中枢神经系统转移患者的中枢神经系统疗效。方法：在这项回顾性研究中，如果患有晚期 ALK 阳性 NSCLC 并伴有大的（定义为≥1 cm）或有症状的 CNS 转移并接受艾乐替尼治疗的患者符合条件。审查医疗记录和放射成像以确定治疗结果。根据修订后的实体瘤反应评估标准 1.1 版评估 CNS 功效。结果：在 19 名患者中，15 (79%) 人在基线时有可测量的 CNS 疾病，可评估反应。这些患者的 CNS 客观反应率为 73.3%（95% 置信区间 [CI]：44.9%–92.2%），CNS 疾病控制率为 100.0%（95% CI：78.2%–100.0%），中位值CNS 反应持续时间为 19.3 个月（95% CI：14.3 个月——不可评估）。在 18 名具有可测量和/或不可测量基线 CNS 疾病的可评估患者中，CNS 客观反应率为 72.2%（95% CI：46.5%–90.3%），CNS 疾病控制率为 100.0%（95% CI：81.5%– 100.0%），中位 CNS 反应持续时间为 17.1 个月（95% CI：14.3 个月——不可评估）。在开始艾乐替尼治疗后，所有 8 名出现症状可归因于 CNS 转移的患者都有临床改善。6 名患者 (32%) 最终需要挽救性脑放疗。结论：