随着多种靶向疗法获批用于治疗间变性淋巴瘤激酶 (ALK) 阳性转移性非小细胞肺癌 (NSCLC)，了解下一代 ALK 酪氨酸激酶抑制剂 (TKI) 各种序列的结果变得越来越重要。我们描述了美国 ALK 阳性 NSCLC 1L 治疗中接受第二代 ALK TKI 治疗的患者的当代测序模式和一线 (1L) 和二线 (2L) 治疗的治疗效果。 2017 年 6 月至 2021 年 4 月期间，在 Flatiron Health 电子健康记录衍生的去识别化数据库中开始接受 1L 艾乐替尼或布加替尼治疗的 ALK 阳性晚期 NSCLC 患者，随访至 2023 年 4 月。1L 和 2L 治疗停止时间 (TTD) 、1L 加 2L 序贯治疗的 TTD (TTD2) 以及序贯 ALK TKI 治疗的总时间（包括超过 2L）进行了评估。患者 (N=273) 的随访中位持续时间为 28.9 个月。在停止 1L 治疗的患者中，22% 的患者在未接受 2L 治疗的情况下在 1L 停止后死亡（从停止到死亡的中位时间为 4.0 个月）。 1L 和 2L 的 TTD 中位数（95% 置信区间 [CI]）分别为 21.9 (15.2-25.8) 和 7.3 (5.3-10.2) 个月。中位 (95% CI) TTD2 为 29.4 (25.1-36.1) 个月，序贯 ALK TKI 治疗的总时间为 28.0 (23.6-32.9) 个月。在这项大型真实世界研究中，TTD2 和序贯 ALK TKI 治疗的总时间为大约 2.5 年。在 ALK 阳性晚期 NSCLC 患者中使用具有最长 1L 有效性的药物，从 1L 到 2L 的高损耗率以及通过 1L 治疗支持观察到的最长临床获益。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

With multiple targeted therapies approved for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), it is increasingly important to understand outcomes with various sequences of next-generation ALK tyrosine kinase inhibitors (TKIs). We describe contemporary sequencing patterns and treatment effectiveness of first-line (1L) and second-line (2L) treatments in patients who received second-generation ALK TKIs in the 1L treatment of ALK-positive NSCLC in the United States.A cohort of adults with ALK-positive advanced NSCLC who initiated treatment with 1L alectinib or brigatinib between June 2017 and April 2021 in the Flatiron Health electronic health record-derived de-identified database were followed through April 2023. Time to treatment discontinuation (TTD) in 1L and 2L, TTD on 1L plus 2L sequential therapy (TTD2), and total time on sequential ALK TKI therapy (including beyond 2L) were evaluated.Patients (N=273) were followed up for a median duration of 28.9 months. Among patients who discontinued 1L therapy, 22% died after 1L discontinuation (median time from discontinuation to death, 4.0 months) without receiving 2L therapy. Median (95% confidence interval [CI]) TTD was 21.9 (15.2-25.8) and 7.3 (5.3-10.2) months in 1L and 2L, respectively. Median (95% CI) TTD2 was 29.4 (25.1-36.1) months and total time on sequential ALK TKI treatment was 28.0 (23.6-32.9) months.In this large real-world study, TTD2 and the total time on sequential ALK TKIs was approximately 2.5 years. The high attrition rate from 1L to 2L and the longest clinical benefit observed with 1L therapy support using the drug with the longest 1L effectiveness up front in patients with ALK-positive advanced NSCLC.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.