ALTA-1L第三期开放标签试验表明，与曲妥珠单抗相比，布里加替尼延长了ALK阳性局部晚期或转移性非小细胞肺癌患者未接受ALK靶向治疗的无进展生存期（PFS）。本后续分析利用ALTA-1L试验的数据，采用质量调整（QA）的无疾病或毒性症状时间（Q-TWiST）方法，在这种患者群体中比较了布里加替尼相对于曲妥珠单抗的QA生存益处。Q-TWiST分析使用了布里加替尼（n = 137）和曲妥珠单抗（n = 138）的最终（2021年1月29日）个体患者级别的盲目独立评审委员会（BIRC）和研究者评估的生存数据。向未接受ALK靶向治疗的ALK阳性局部晚期或转移性非小细胞肺癌的成年患者（N = 275）进行了比较。比较了两种治疗方法的Q-TWiST。对基线时是否存在脑转移等各种临床病理特征进行亚组分析。布里加替尼与曲妥珠单抗相比，无病或无毒性症状的时间显著延长（P < 0.001），Q-TWiST也显著增加（平均[标准误]月：BIRC评估，28.2 [1.2]与25.1 [1.1]，P = 0.045; 研究者评估，28.5 [1.2]与24.8 [1.1]，P = 0.018）。相对于曲妥珠单抗，布里加替尼的Q-TWiST增益具有临床意义（BIRC评估，10.4%; 研究者评估，12.3%）。在基线时存在脑转移并接受布里加替尼治疗的患者的Q-TWiST显著增加（平均[标准误]月：BIRC评估，29.0 [1.9]与19.0 [1.9]，P = 0.0001）相对于接受曲妥珠单抗的患者。一线布里加替尼治疗与ALK阳性局部晚期或转移性非小细胞肺癌患者的Q-TWiST在临床和统计学上均达到显著意义，支持ALTA-1L试验结果，并证明布里加替尼是一种安全有效的一线治疗ALK阳性非小细胞肺癌方法。版权所有©2023 Elsevier B.V.发表。

The ALTA-1L phase 3 open-label trial demonstrated increased progression-free survival (PFS) with brigatinib versus crizotinib in patients with anaplastic lymphoma kinase-positive (ALK-positive) locally advanced or metastatic non-small cell lung cancer (NSCLC) previously untreated with ALK-targeted therapy. This post-hoc analysis of data from the ALTA-1L trial used the quality-adjusted (QA) time without symptoms of disease or toxicity (Q-TWiST) methodology to compare the QA survival benefit of brigatinib versus crizotinib in this patient population.The Q-TWiST analysis was performed using final (January 29, 2021) individual patient-level blinded independent review committee (BIRC)- and investigator-assessed survival data for brigatinib (n = 137) and crizotinib (n = 138) in adult patients (N = 275) with ALK-positive locally advanced or metastatic NSCLC previously untreated with ALK-targeted therapy. Q-TWiST was compared between the two treatments. Subgroup analyses were performed in patients stratified by various clinicopathological characteristics, including presence or absence of brain metastases at baseline.Brigatinib was associated with significantly longer time without symptoms of disease or toxicity (P < 0.001) than crizotinib, with significantly greater Q-TWiST (mean [SE] months: BIRC-assessed, 28.2 [1.2] versus 25.1 [1.1], P = 0.045; investigator-assessed, 28.5 [1.2] versus 24.8 [1.1], P = 0.018). Relative gains in Q-TWiST with brigatinib compared to crizotinib were clinically meaningful (BIRC-assessed, 10.4%; investigator-assessed, 12.3%). Patients with brain metastases at baseline receiving brigatinib had significantly greater Q-TWiST (mean [SE] months: BIRC-assessed, 29.0 [1.9] versus 19.0 [1.9], P = 0.0001) than those receiving crizotinib.First-line brigatinib treatment was associated with significant and clinically meaningful gains in Q-TWiST compared to crizotinib in patients with ALK-positive locally advanced or metastatic NSCLC, supporting the results of the ALTA-1L trial and brigatinib as a safe and effective first-line treatment for ALK-positive NSCLC.Copyright © 2023. Published by Elsevier B.V.