Brigatinib 是一种针对 ALK 和 ROS1 的下一代酪氨酸激酶抑制剂 (TKI)。 Barossa 研究是一项针对 ROS1 重排实体瘤患者进行 brigatinib 的多中心、II 期篮子研究。未接受过 ROS1 TKI 治疗的 ROS1 重排非小细胞肺癌 (NSCLC) 患者被纳入队列 1，之前接受过克唑替尼治疗的 ROS1 重排 NSCLC 患者被纳入队列 2。 NSCLC 被纳入队列 3。符合条件的患者接受布加替尼治疗，剂量为 180 毫克，每天一次，并有 7 天的导入期，剂量为 90 毫克。主要终点是通过独立中央审查在队列 1 和队列 2 中评估的客观缓解率 (RECIST 1.1)。2019 年 7 月至 2021 年 6 月期间，有 51 名患者参加了该研究。在这 51 名患者中，47 名患者患有 ROS1 重排的 NSCLC；其中 28 名和 19 名患者分别被纳入队列 1 和队列 2。其余4名患者患有其他ROS1重排的实体瘤，包括直肠肿瘤、脑肿瘤和胰腺肿瘤各1名，以及原发性未知肿瘤1名。队列 1（未接受过 TKI 治疗的 NSCLC 患者）中确认的客观缓解率为 71.4% [95% CI 51.3% 至 86.8%]，队列 2（NSCLC 患者）中的客观缓解率为 31.6%（95% CI 12.6% 至 56.6%）既往接受过克唑替尼治疗的患者）。第 1 组的中位无进展生存期为 12.0 个月（95% CI 5.5-22.9 个月），第 2 组的中位无进展生存期为 7.3 个月（95% CI 1.3-17.5 个月）。第 3 组中没有患者显示出任何治疗反应。 9.8% 的患者出现肺炎。布加替尼对于未接受过 TKI 治疗的 ROS1 重排 NSCLC 患者有效。布加替尼的安全性与之前的研究报告一致。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Brigatinib is a next-generation tyrosine kinase inhibitor (TKI) targeting ALK and ROS1. The Barossa study is a multicenter, phase II basket study of brigatinib in patients with ROS1-rearranged solid tumors. ROS1 TKI-naive patients with ROS1-rearranged non-small-cell lung cancer (NSCLC) were enrolled in cohort 1, and ROS1-rearranged NSCLC patients treated previously with crizotinib were enrolled in cohort 2. Patients with ROS1-rearranged solid tumors other than NSCLC were enrolled in cohort 3.Eligible patients received brigatinib at the dose of 180 mg once daily with a 7-day lead-in period at 90 mg. The primary endpoint was the objective response rate (RECIST 1.1) assessed by independent central review in cohorts 1 and 2.Between July 2019 and June 2021, 51 patients were enrolled into the study. Of the 51, 47 patients had ROS1-rearranged NSCLC; 28 and 19 of these patients were enrolled in cohort 1 and cohort 2, respectively. The remaining four patients had other ROS1-rearranged solid tumors, including rectal, brain, and pancreas tumor in one patient each, and primary unknown tumor in one patient. The confirmed objective response rate was 71.4% [95% confidence interval (CI) 51.3% to 86.8%] in cohort 1 (TKI-naive NSCLC patients) and 31.6% (95% CI 12.6% to 56.6%) in cohort 2 (NSCLC patients treated previously with crizotinib). The median progression-free survival was 12.0 months (95% CI 5.5-22.9 months) in cohort 1 and 7.3 months (95% CI 1.3-17.5 months) in cohort 2. None of the patients in cohort 3 showed any treatment response. Pneumonitis was observed in 9.8% of all the patients.Brigatinib was effective in TKI-naive patients with ROS1-rearranged NSCLC. The safety profile of brigatinib was consistent with that reported from previous studies.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.