奥莫替尼（HS-10296）治疗晚期EGFR T790M+非小细胞肺癌患者的疗效：APOLLO注册试验中国家药品监督管理局批准后的更新结果
Efficacy of Aumolertinib (HS-10296) in Patients With Advanced EGFR T790M+ NSCLC: Updated Post-National Medical Products Administration Approval Results From the APOLLO Registrational Trial.
作者信息
Lu Shun, Wang Qiming, Zhang Guojun, Dong Xiaorong, Yang Cheng-Ta, Song Yong, Chang Gee-Chen, Lu You, Pan Hongming, Chiu Chao-Hua, Wang Zhehai, Feng Jifeng, Zhou Jianying, Xu Xingxiang, Guo Renhua, Chen Jianhua, Yang Haihua, Chen Yuan, Yu Zhuang, Shiah Her-Shyong, Wang Chin-Chou, Yang Nong, Fang Jian, Wang Ping, Wang Kai, Hu Yanping, He Jianxing, Wang Ziping, Shi Jianhua, Chen Shaoshui, Wu Qiong, Sun Changan, Li Chuan, Wei Hongying, Cheng Ying, Su Wu-Chou, Hsia Te-Chun, Cui Jiuwei, Sun Yuping, Ou Sai-Hong Ignatius, Zhu Viola W, Chih-Hsin Yang James
机构信息
Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Department of Internal Medicine, Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, People's Republic of China.
出版信息
J Thorac Oncol. 2022 Mar;17(3):411-422. doi: 10.1016/j.jtho.2021.10.024. Epub 2021 Nov 19.
INTRODUCTION
Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) with revealed activity against EGFR-sensitizing mutations and EGFR T790M mutation.
METHODS
Patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy were enrolled in this registrational phase 2 trial of aumolertinib at 110 mg orally once daily (NCT02981108). The primary end point was objective response rate (ORR) by independent central review.
RESULTS
A total of 244 patients with EGFR T790M-positive NSCLC were enrolled. The ORR by independent central review was 68.9% (95% confidence interval [CI]: 62.6-74.6). The disease control rate was 93.4% (95% CI: 89.6-96.2). The median duration of response was 15.1 months (95% CI: 12.5-16.6). The median progression-free survival was 12.4 months (95% CI: 9.7-15.0). Among 23 patients with assessable central nervous system (CNS) metastases, the CNS-ORR and CNS-disease control rate were 60.9% (95% CI: 38.5-80.3) and 91.3% (95% CI: 72.0-98.9), respectively. The median CNS-duration of response was 12.5 months (95% CI: 5.6-not reached). Treatment-related adverse events of more than or equal to grade 3 occurred in 16.4% of the patients, with the most common being increased blood creatine phosphokinase level (7%) and increased alanine aminotransferase level (1.2%). The relative dose density of aumolertinib was 99.2% in this study.
CONCLUSIONS
Aumolertinib is an effective and well-tolerated third-generation EGFR TKI for patients with EGFR T790M-positive advanced NSCLC after disease progression on first- and second-generation EGFR TKI therapy. On the basis of these findings, aumolertinib was approved in the People's Republic of China for patients positive for EGFR T790M NSCLC.
简介
奥莫替尼（曾用名阿美替尼；HS-10296）是一种新型第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI），对EGFR敏感突变和EGFR T790M突变均有活性。
方法
在这项奥莫替尼的注册性2期试验中，纳入了在第一代或第二代EGFR TKI治疗进展后出现EGFR T790M突变的局部晚期或转移性非小细胞肺癌（NSCLC）患者，口服奥莫替尼110mg，每日1次（NCT02981108）。主要终点为独立中心审查的客观缓解率（ORR）。
结果
共纳入244例EGFR T790M阳性NSCLC患者。独立中心审查的ORR为68.9%（95%置信区间[CI]：62.6-74.6）。疾病控制率为93.4%（95%CI：89.6-96.2）。中位缓解持续时间为15.1个月（95%CI：12.5-16.6）。中位无进展生存期为12.4个月（95%CI：9.7-15.0）。在23例可评估的中枢神经系统（CNS）转移患者中，CNS-ORR和CNS-疾病控制率分别为60.9%（95%CI：38.5-80.3）和91.3%（95%CI：72.0-98.9）。中位CNS缓解持续时间为12.5个月（95%CI：5.6-未达到）。3级及以上治疗相关不良事件发生在16.4%的患者中，最常见的是血肌酸磷酸激酶水平升高（7%）和谷丙转氨酶水平升高（1.2%）。本研究中奥莫替尼的相对剂量强度为99.2%。
结论
对于第一代和第二代EGFR TKI治疗疾病进展后的EGFR T790M阳性晚期NSCLC患者，奥莫替尼是一种有效且耐受性良好的第三代EGFR TKI。基于这些研究结果，奥莫替尼在中国被批准用于EGFR T790M NSCLC阳性患者。
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