泰瑞替尼治疗中国非小细胞肺癌患者的疗效和安全性：TRUST-I 期研究。
Efficacy and Safety of Taletrectinib in Chinese Patients With Non-Small Cell Lung Cancer: The Phase II TRUST-I Study.
机构信息
Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
出版信息
J Clin Oncol. 2024 Aug 1;42(22):2660-2670. doi: 10.1200/JCO.24.00731. Epub 2024 Jun 1.
PURPOSE
Taletrectinib, a highly potent, CNS-active, tyrosine kinase inhibitor (TKI), has demonstrated high and durable response rates, high intracranial objective response rate (ORR), prolonged progression-free survival (PFS), and activity against G2032R with a favorable safety profile. We report outcomes from the pivotal TRUST-I study (ClinicalTrials.gov identifier: NCT04395677) of taletrectinib for non-small cell lung cancer in China.
METHODS
TRUST-I evaluated TKI-naїve and crizotinib-pretreated patients. The primary end point was confirmed ORR (cORR) by independent review committee; key secondary end points included duration of response (DOR), PFS, and safety.
RESULTS
As of November 2023, 173 patients were enrolled (median age, 55 years; 58% female; 73% never smoked; TKI naїve: n = 106; crizotinib pretreated: n = 67). In TKI-naїve patients, cORR and intracranial cORR were 91% and 88%, respectively, and 52% and 73% in crizotinib-pretreated patients. In TKI-naїve patients, median DOR and median PFS were not reached (NR) with 22.1-month and 23.5-month follow-up, respectively. In crizotinib-pretreated patients, the median DOR was 10.6 months (95% CI, 6.3 months to NR; 8.4-month follow-up), and the median PFS was 7.6 months (95% CI, 5.5 to 12.0 months; 9.7-month follow-up). Eight of 12 patients (67%) with G2032R mutations responded. The most frequent treatment-emergent adverse events (TEAEs) were increased AST (76%), diarrhea (70%), and increased ALT (68%), most of which were grade 1-2. Incidences of neurologic TEAEs were low (dizziness: 23%; dysgeusia: 10%) and mostly grade 1. Discontinuations (5%) and dose reductions (19%) due to TEAEs were low.
CONCLUSION
Taletrectinib continues to show high and durable overall responses, prolonged PFS, robust activity against intracranial lesions and acquired resistance mutations including G2032R, and a favorable safety profile with a low incidence of neurologic TEAEs.
目的
塔列替尼是一种高效能、中枢神经系统活性的酪氨酸激酶抑制剂（TKI），具有高且持久的缓解率、高颅内客观缓解率（ORR）、延长无进展生存期（PFS）和对 G2032R 的活性，且安全性良好。我们报告了在中国进行的非小细胞肺癌塔列替尼关键性 TRUST-I 研究（ClinicalTrials.gov 标识符：NCT04395677）的结果。
方法
TRUST-I 评估了 TKI 初治和克唑替尼预处理的患者。主要终点为独立审查委员会确认的缓解率（cORR）；关键次要终点包括缓解持续时间（DOR）、PFS 和安全性。
结果
截至 2023 年 11 月，共纳入 173 例患者（中位年龄 55 岁；58%为女性；73%从不吸烟；TKI 初治：n=106；克唑替尼预处理：n=67）。在 TKI 初治患者中，cORR 和颅内 cORR 分别为 91%和 88%，在克唑替尼预处理患者中分别为 52%和 73%。在 TKI 初治患者中，中位 DOR 和中位 PFS 尚未达到（NR），随访时间分别为 22.1 个月和 23.5 个月。在克唑替尼预处理患者中，中位 DOR 为 10.6 个月（95%CI：6.3 个月至 NR；8.4 个月随访），中位 PFS 为 7.6 个月（95%CI：5.5 至 12.0 个月；9.7 个月随访）。12 例（67%）携带 G2032R 突变的患者中有 8 例（67%）有缓解。最常见的治疗相关不良事件（TEAEs）为 AST 升高（76%）、腹泻（70%）和 ALT 升高（68%），大多数为 1-2 级。神经 TEAEs 的发生率较低（头晕：23%；味觉障碍：10%），大多数为 1 级。由于 TEAEs 导致的停药（5%）和剂量减少（19%）发生率较低。
结论
塔列替尼继续表现出高且持久的总体缓解率、延长的 PFS、对颅内病变和获得性耐药突变（包括 G2032R）的强大活性，以及较低的神经 TEAEs 发生率和良好的安全性。
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