Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: A pooled analysis of two clinical studies

作者：Yang, Sheng; Wu, Shiman; Zhao, Yanqiu; Chen, Gongyan; Zhu, Bo; Li, Xingya; Wang, Ke; Shi, Jianhua; Cang, Shundong; Yao, Wenxiu; Fan, Yun; Fang, Jian; Zhang, Liangming; Zhou, Jianying; Wu, Lin; Zheng, Rongsheng; Huang, Meijuan; Pan, Yueyin; Yang, Zhixiong; Sun, Meili; Yu, Huiqing; Wang, Donglin; Huang, Jianan; Wang, Lijun; Shu, Yongqian; Chen, Zhaohong; Liu, Chunling; Li, Jingzhang; Liu, Jiwei; Sun, Shenghua; Guo, Yanzhen; Meng, Zili; Liu, Zhefeng; Han, Zhigang; Wu, Gang; Lu, Hong; Ma, Rui

来源：Lung Cancer, 2023, 180: 107194.

DOI：10.1016/j.lungcan.2023.107194

• Rezivertinib
• BPI-7711
• EGFR T790M mutation
• CNS
• NSCLC

Background: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyro-sine kinase inhibitor (TKI) which revealed the systematic and central nervous system (CNS) antitumor activities for EGFR T790M-mutated advanced NSCLC in previous clinical studies and is further analyzed here.Methods: Eligible patients from the previous phase I and phase IIb studies of rezivertinib were included for pooled analysis. Post-progressive patients who received a prescribed dosage (& GE;180 mg) of rezivertinib orally once daily were included in full analysis set (FAS), while those with stable, asymptomatic CNS lesions, including measurable and non-measurable ones at baseline were included in CNS full analysis set (cFAS). Patients with measurable CNS lesions were included in CNS evaluable for response set (cEFR). BICR-assessed CNS objective response rate (CNS-ORR), CNS disease control rate (CNS-DCR), CNS duration of response (CNS-DoR), CNS progression-free survival (CNS-PFS), and CNS depth of response (CNS-DepOR) were evaluated.Results: 355 patients were included in FAS, among whom 150 and 45 patients were included in cFAS and cEFR. This pooled analysis showed the CNS-ORR was 32.0% (48/150; 95% CI: 24.6-40.1%) and the CNS-DCR was 42.0% (63/150; 95% CI: 34.0-50.3%) in cFAS, while that in cEFR were 68.9% (31/45; 95% CI: 53.4-81.8%) and 100% (45/45; 95% CI: 92.1-100.0%). In cEFR, the median CNS-DepOR and the mean of CNS-DepOR were-52.0% (range:-100.0 to 16.1%) and-46.8% (95% CI: -55.5 to-38.1%). In cFAS, the median CNS-DoR and CNS-PFS were 13.8 (95% CI: 9.6-not calculable [NC]) and 16.5 (95% CI: 13.7-NC) months.Conclusions: Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.

• 单位
  中国科学院研究生院; 浙江大学; 中国医学科学院; 重庆大学; 汕头大学; 苏州大学; 山东大学; 哈尔滨医科大学; 郑州大学; 安徽医科大学; 四川大学; 华中科技大学; 中国医学科学院北京协和医院; 广东医学院