SCI

20 June 2024

Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non–Small Cell Lung Cancer: The Phase II TRUST-I Study

（J Clin Oncol；IF: 45.4）

  • Li W, Xiong A, Yang N et al. Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study. J Clin Oncol Jco2400731, 2024

  • Correspondence to: Caicun Zhou, MD, PhD; e-mail: caicunzhoudr@163.com.

PURPOSE 目的

Taletrectinib, a highly potent, CNS-active, ROS1 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 ROS1+ non–small cell lung cancer in China.

Taletrectinib是一种高效、具有中枢神经系统活性的ROS1酪氨酸激酶抑制剂(TKI)，已显示出高且持久的缓解率、较高颅内客观缓解率(ORR)、较长的无进展生存期(PFS)，以及对G2032R有活性，并且具有良好的安全性。我们报告了taletrectinib在中国治疗ROS1+非小细胞肺癌的TRUST-I研究的结局(ClinicalTrials.gov识别号:NCT04395677)。

 

METHODS 方法

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.

TRUST-I评估了TKI初治和克唑替尼治疗过的患者。主要终点为经独立审查委员会确认的ORR (cORR);关键次要终点包括缓解持续时间(DOR)、PFS和安全性。

 

RESULTS 结果

As of November 2023, 173 patients were enrolled (median age, 55 years; 58% female; 73% never smoked; TKI naїve: n=5106; crizotinib pretreated: n=567). 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.

截至2023年11月，本试验纳入了173例患者(中位年龄，55岁;58%的女性;73%从不吸烟;TKI 初治: n=5106;克唑替尼预处理:567例)。在TKI初治患者中，cORR和颅内cORR分别为91%和88%，在接受过克唑替尼治疗的患者中，分别为52%和73%。TKI初治例患者中位DOR为22.1个月，中位PFS为23.5个月，均未达到NR。在接受过克唑替尼治疗的患者中，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 ~ 12.0个月;9.7个月随访)。在携带G2032R突变的12例患者中，有8例(67%)缓解。最常见的不良反应为AST升高(76%)、腹泻(70%)和ALT升高(68%)，且多为1 ~ 2级。神经系统治疗相关不良反应的发生率较低(头晕:23%;味觉障碍:10%)，多为1级。治疗相关不良反应导致的停药(5%)和剂量降低(19%)发生率较低。

 

CONCLUSION 结论

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.

Taletrectinib继续表现出高且持久的总缓解率、较长的PFS、对颅内病变和包括G2032R在内的获得性耐药突变的稳健活性，以及良好的安全性(神经系统治疗相关不良反应的发生率低)。