Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial
Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial
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DOI：
10.1016/j.jtho.2019.11.004
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发表时间：
2020-03-01
影响因子：
20.4
通讯作者：
Camidge, D. Ross
中科院分区：
文献类型：
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作者：
Huber, Rudolf M.;Hansen, Karin H.;Camidge, D. Ross
我们报告了一项评估布加替尼治疗克唑替尼难治性间变性淋巴瘤激酶阳性NSCLC的2期随机研究的最新数据。方法：根据中枢神经系统（CNS）转移和对克唑替尼的最佳反应，患者按1:1随机分组，口服布加替尼90mg，每日一次（A组）或180mg，每日一次（B组），7天引入90mg （B组）。主要终点是研究者根据实体肿瘤反应评价标准1.1版评估确定的客观反应率。次要终点包括独立审查委员会（IRC）评估的无进展生存期（PFS）、颅内PFS （iPFS）和总生存期（OS）。探索性分析包括中枢神经系统与前中枢神经系统靶病变反应以及反应深度与PFS和OS的相关性。结果：222名随机患者（A组112名，B组110名）中，59名（27%）在分析时仍在使用布加替尼（中位随访：19.6个月对24.3个月）。在基线时，A组和B组分别有71%和67%的脑损伤。研究者评估确认的客观缓解率为46%对56%。irc评估的PFS中位数为9.2个月（95%可信区间：7.4-12.8），而16.7个月（11.6-21.4）。中位OS为29.5个月（18.2个未达到）vs 34.1个月（27.7个未达到）。irc确认的基线脑病变患者的颅内客观缓解率为50%（26例中的13例）对67%（18例中的12例）；颅内反应的中位持续时间分别为9.4个月和16.6个月。irc评估的iPFS分别为12.8和18.4个月。在两组中，目标病灶缩小率为1%-25%、26% - 50%、51%-75%和76%-100%的患者，irc评估的中位PFS分别为1.9、5.5、11.1、16.7和15.6个月。在更长时间的随访中没有观察到新的安全性发现。结论：布里加替尼（180mg，每日1次，带铅）在克唑替尼难治性患者中继续表现出强劲的PFS，较长的iPFS和颅内反应持续时间，以及高的颅内客观缓解率。在未来的靶向治疗试验中，反应深度可能是一个重要的终点。(C) 2019年国际肺癌研究协会。Elsevier Inc.出版。
Introduction: We report updated data from a phase 2 randomized study evaluating brigatinib in crizotinib-refractory anaplastic lymphoma kinase-positive NSCLC.Methods: Patients were randomized 1:1 to take either oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (arm B), stratified by central nervous system (CNS) metastases and best response to crizotinib. The primary end point was investigator-assessed confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included independent review committee (IRC)-assessed progression-free survival (PFS), intracranial PFS (iPFS), and overall survival (OS). Exploratory analyses included CNS versus ex-CNS target lesion response and correlation of depth of response with PFS and OS.Results: Among 222 randomized patients (112 and 110 in arms A and B, respectively), 59 (27%) remained on brigatinib at analysis (median follow-up: 19.6 versus 24.3 months). At baseline, 71% and 67% had brain lesions among A and B arms, respectively. Investigator-assessed confirmed objective response rate was 46% versus 56%. Median IRC-assessed PFS was 9.2 months (95% confidence interval: 7.4-12.8) versus 16.7 months (11.6-21.4). Median OS was 29.5 months (18.2-not reached) versus 34.1 months (27.7-not reached). IRC-confirmed intracranial objective response rate in patients with measurable baseline brain lesions was 50% (13 of 26) versus 67% (12 of 18); median duration of intracranial response was 9.4 versus 16.6 months. IRC-assessed iPFS was 12.8 versus 18.4 months. Across arms, median IRC-assessed PFS was 1.9, 5.5, 11.1, 16.7, and 15.6 months for patients with no, 1%-25%, 26%50%, 51%-75%, and 76%-100% target lesion shrinkage, respectively. No new safety findings were observed with longer follow-up.Conclusions: Brigatinib (180 mg once daily with lead-in) continues to demonstrate robust PFS, long iPFS and duration of intracranial response, and high intracranial objective response rate in crizotinib-refractory patients. Depth of response may be an important end point to capture in future targeted therapy trials. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc.