Befotertinib 用于治疗已接受过 EGFR T790M 突变的局部晚期或转移性 NSCLC 患者：2 期试验的最终总生存率结果。
Befotertinib for patients with pretreated EGFR T790M mutated locally advanced or metastatic NSCLC: Final overall survival results from a phase 2 trial.
发表日期：2024 Jul 27
作者：
Shun Lu, Yiping Zhang, Guojun Zhang, Jianying Zhou, Shundong Cang, Ying Cheng, Gang Wu, Peiguo Cao, Dongqing Lv, Hong Jian, Xiangming Jin, Chengshui Chen, Panwen Tian, Kai Wang, Guanming Jiang, Gongyan Chen, Qun Chen, Hui Zhao, Cuimin Ding, Renhua Guo, Guoping Sun, Bin Wang, Liyan Jiang, Zhe Liu, Jian Fang, Junquan Yang, Wu Zhuang, Yunpeng Liu, Jian Zhang, Yueyin Pan, Jun Chen, Qitao Yu, Min Zhao, Jiuwei Cui, Dianming Li, Tienan Yi, Zhuang Yu, Yan Yang, Yan Zhang, Xiuyi Zhi, Yunchao Huang, Rong Wu, Liangan Chen, Aimin Zang, Lejie Cao, Qingshan Li, Xiaoling Li, Yong Song, Donglin Wang, Shucai Zhang, Lieming Ding, Ling Zhang, Dong Ji, Zhilin Shen
来源：
LUNG CANCER
摘要：
在一项关键 2 期单臂研究 (NCT03861156) 的初步分析中，befotertinib (D-0316) 在接受过 EGFR T790M 突变非小细胞肺癌 (NSCLC) 治疗的患者中显示出临床益处和可控的安全性，包括那些患有脑转移的患者。符合条件的患者每天一次口服 50 mg（A 组）或 75-100 mg（B 组）贝福特替尼，直至疾病进展、撤回知情同意书或死亡。初步分析的主要终点是由独立审查委员会评估的客观缓解率 (ORR)。 OS 和安全性是次要终点。在此，我们提供最终的 OS 和安全性数据。 A 组中共有 176 名患者，B 组中共有 290 名患者最终入组。截至数据截止日期（2023 年 5 月 31 日），队列 A 的中位随访时间为 47.9 个月（95% CI：47.1-48.3），队列 B 为 36.7 个月（35.9-37.9）。中位 OS 为 23.9 个月队列 A 中为 (95% CI: 21.1-27.2)，队列 B 中为 31.5 个月 (26.8-35.3)。队列 A 中患有和不患有脑转移的患者的中位 OS 为 18.6 个月 (95% CI: 14.9-26.3)，分别为 26.4 个月（95% CI：23.0-29.0）。在队列 B 中，这些数据分别为 23.0 个月（95% CI：18.6-29.1）和 35.5 个月（95% CI：29.3-NE）。贝福特替尼的安全性与之前的数据保持一致。 3 级或以上治疗引起的不良事件在 A 组中为 38.1%，在 B 组中为 50.3%，其中 22.2% 和 31.7% 与研究药物相关。与其他第 3 代相比，Befotertinib 表现出更深远的 OS 获益EGFR TKI，尽管有交叉试验数据比较，但应谨慎解释。安全性是可控的，并且与先前报告的已确诊 T790M 突变阳性 NSCLC 患者的预处理数据一致。版权所有 © 2024。由 Elsevier B.V. 出版。
In the initial analysis of a pivotal phase 2 single-arm study (NCT03861156), befotertinib (D-0316) showed clinical benefit with a manageable safety profile in pretreated patients with EGFR T790M mutated non-small cell lung cancer (NSCLC), including those with brain metastases.Eligible patients received oral befotertinib of 50 mg (cohort A) or 75-100 mg (cohort B) once daily until disease progression, withdrawal of informed consent, or death. The primary endpoint for the initial analysis was objective response rate (ORR) assessed by an independent review committee. OS and safety were secondary endpoints. Herein, we present the final OS and safety data.A total of 176 patients in cohort A and 290 patients in cohort B were finally enrolled. At data cutoff (May 31, 2023), the median duration of follow-up was 47.9 months (95 % CI: 47.1-48.3) in cohort A and 36.7 months (35.9-37.9) in cohort B. The median OS was 23.9 months (95 % CI: 21.1-27.2) in cohort A and 31.5 months (26.8-35.3) in cohort B. The median OS for patients with and without brain metastasis in cohort A was 18.6 months (95 % CI: 14.9-26.3) and 26.4 months (95 % CI: 23.0-29.0), respectively. In cohort B, these data was 23.0 months (95 % CI: 18.6-29.1) and 35.5 months (95 % CI: 29.3-NE), respectively. The safety profile of befotertinib remained consistent with previous data. Grade 3 or higher treatment-emergent adverse events were 38.1 % in the cohort A and 50.3 % in the cohort B, and 22.2 % and 31.7 % were related to the study drug.Befotertinib demonstrated a more profound OS benefit compared to other 3rd-generation EGFR TKI, despite that cross trial data comparison should be interpreted with caution. The safety profile was manageable and consistent with previously report data in pretreated patients with confirmed T790M mutation-positive NSCLC.Copyright © 2024. Published by Elsevier B.V.