一种新型第三代 EGFR 酪氨酸激酶抑制剂阿维替尼治疗 EGFR T790M 突变型非小细胞肺癌：一项多中心 I/II 期研究。
A Novel Third-generation EGFR Tyrosine Kinase Inhibitor Abivertinib for EGFR T790M-mutant Non-Small Cell Lung Cancer: a Multicenter Phase I/II Study.
机构信息
Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
Department of Medical Oncology, Second Chest Cancer Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
出版信息
Clin Cancer Res. 2022 Mar 15;28(6):1127-1135. doi: 10.1158/1078-0432.CCR-21-2595.
PURPOSE
To establish recommended phase II dose (RP2D) in phase I and evaluate safety and efficacy of abivertinib in patients with EGFR Thr790Met point mutation (T790M)-positive(+) non-small cell lung cancer (NSCLC) with disease progression from prior EGFR inhibitors in phase II.
PATIENTS AND METHODS
This multicenter, open-label study included 367 adult Chinese patients. Abivertinib at doses of 50 mg twice a day to 350 mg twice a day was evaluated in phase I in continual 28-day cycles, and the RP2D of 300 mg twice a day was used in phase II in continual 21-day cycles. Primary endpoints include RP2D in phase I and objective response rate (ORR) at RP2D in phase II.
RESULTS
The RP2D of 300 mg twice a day for abivertinib was established based on pharmacokinetics, efficacy, and safety profiles across doses in phase I. In phase II, 227 patients received RP2D for a median treatment duration of 24.6 weeks (0.43-129). Among 209 response-evaluable patients, confirmed ORR was 52.2% [109/209; 95% confidence interval (CI): 45.2-59.1]. Disease control rate (DCR) was 88.0% (184/209; 95% CI: 82.9-92.1). The median duration of response (DoR) and progression-free survival (PFS) was 8.5 months (95% CI: 6.1-9.2) and 7.5 months (95% CI: 6.0-8.8), respectively. The median overall survival (OS) was 24.9 months [95% CI: 22.4-not reachable (NR)]. All (227/227) patients reported at least 1 adverse event (AE), with 96.9% (220/227) of treatment-related AEs. Treatment-related serious AEs were reported in 13.7% (31/227) of patients. Death was reported in 4.4% (10/227) of patients, and none was deemed as treatment-related.
CONCLUSIONS
Abivertinib of 300 mg twice a day demonstrated favorable clinical efficacy with manageable side effects in patients with EGFR T790M+ NSCLC.
目的
在 I 期研究中确定 I 期的推荐 II 期剂量（RP2D），并评估 abivertinib 在先前接受 EGFR 抑制剂治疗后疾病进展的 EGFR Thr790Met 点突变（T790M）阳性（+）非小细胞肺癌（NSCLC）患者中的安全性和疗效。
患者和方法
这是一项多中心、开放性研究，纳入了 367 名成年中国患者。abivertinib 的剂量为每天两次 50mg 至每天两次 350mg，在 I 期连续 28 天周期中进行评估，在 II 期连续 21 天周期中使用 RP2D 为每天两次 300mg。主要终点包括 I 期的 RP2D 和 II 期 RP2D 的客观缓解率（ORR）。
结果
基于 I 期各剂量的药代动力学、疗效和安全性特征，确定了 abivertinib 的 300mg 每天两次的 RP2D。在 II 期，227 名患者接受了 RP2D 治疗，中位治疗持续时间为 24.6 周（0.43-129）。在 209 名可评估反应的患者中，确认的 ORR 为 52.2%（109/209；95%置信区间[CI]：45.2-59.1）。疾病控制率（DCR）为 88.0%（184/209；95%CI：82.9-92.1）。缓解持续时间（DoR）和无进展生存期（PFS）的中位值分别为 8.5 个月（95%CI：6.1-9.2）和 7.5 个月（95%CI：6.0-8.8）。中位总生存期（OS）为 24.9 个月[95%CI：22.4-NR]。所有（227/227）患者均报告至少 1 次不良事件（AE），96.9%（220/227）的治疗相关 AE。13.7%（31/227）的患者报告了治疗相关严重 AE。4.4%（10/227）的患者报告死亡，均与治疗无关。
结论
在 EGFR T790M+ NSCLC 患者中，abivertinib 的每日两次 300mg 剂量显示出良好的临床疗效，副作用可管理。
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