Taletrectinib 与第一代 TKI 在未接受过 TKI 治疗的 ROS1+ 非小细胞肺癌中的疗效比较：一项匹配调整间接比较
Comparative efficacy of taletrectinib versus first-generation TKIs in TKI-naïve ROS1+ non-small cell lung cancer: A matching-adjusted indirect comparison.
作者
作者单位
- University of California Irvine School of Medicine and Chao Family Comprehensive Cancer Center, Orange, CA, USA. Electronic address: nagasakm@hs.uci.edu.
- Princess Margaret Cancer Centre, Temerty School of Medicine, University of Toronto, Toronto, ON, Canada.
- Centre Léon Bérard, Lyon, France.
- Nuvation Bio Inc., New York, NY, USA.
- UC San Diego Moores Cancer Center, San Diego, CA, USA.
- Shanghai East Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
摘要
中文
Taletrectinib 是一种新一代选择性 ROS1 酪氨酸激酶抑制剂（TKI），已被批准用于治疗晚期 ROS1+ 非小细胞肺癌（NSCLC）。由于缺乏直接比较 ROS1 TKI 的头对头试验，我们旨在使用非锚定匹配调整间接比较方法，比较 taletrectinib 与第一代 TKI（克唑替尼和恩曲替尼）在未接受过 TKI 治疗的 ROS1+ NSCLC 患者中的疗效。选取基线协变量对来自 TRUST-I（NCT04395677）和 TRUST-II（NCT04919811）研究的 taletrectinib 汇总数据与克唑替尼和恩曲替尼注册研究的已发表数据进行调整。同时进行了治疗相关不良事件（TRAE）安全性的描述性跨试验比较。调整基线协变量后，与克唑替尼或恩曲替尼相比，taletrectinib 的客观缓解率显著更高，缓解持续时间显著长于恩曲替尼（风险比 [HR]，0.35；95% 置信区间 [CI]，0.21-0.60），无进展生存期显著长于克唑替尼（HR，0.48；95% CI，0.27-0.88）或恩曲替尼（HR，0.42；95% CI，0.27-0.65），总生存期也显著长于克唑替尼（HR，0.34；95% CI，0.15-0.77）或恩曲替尼（HR，0.48；95% CI，0.27-0.88）。敏感性分析结果一致显示 taletrectinib 优于克唑替尼或恩曲替尼。在描述性安全性比较中，taletrectinib、克唑替尼和恩曲替尼的 TRAE 发生率无显著差异。本分析表明，在调整基线特征后，与克唑替尼或恩曲替尼相比，taletrectinib 在未接受过 TKI 治疗的 ROS1+ NSCLC 患者中显示出更优的缓解和生存结局，支持 taletrectinib 作为该类患者人群的有效治疗选择。
English
Taletrectinib is a next-generation, selective ROS1 tyrosine kinase inhibitor (TKI) approved for the treatment of advanced ROS1+ non-small cell lung cancer (NSCLC). In the absence of head-to-head trials comparing ROS1 TKIs, we aimed to compare the efficacy of taletrectinib with first-generation TKIs, crizotinib and entrectinib, in TKI-naïve patients with ROS1+ NSCLC using an unanchored matching-adjusted indirect comparison. Selected baseline covariates were used for adjustment between pooled taletrectinib data from the TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies and published data from the registrational crizotinib and entrectinib studies. A descriptive cross-trial comparison of safety for treatment-related adverse events (TRAEs) was also conducted. After adjustment for baseline covariates, taletrectinib was associated with significantly higher odds of objective response versus crizotinib or entrectinib, significantly longer duration of response versus entrectinib (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.21-0.60), significantly longer progression-free survival versus crizotinib (HR, 0.48; 95% CI, 0.27-0.88) or entrectinib (HR, 0.42; 95% CI, 0.27-0.65), and significantly longer overall survival versus crizotinib (HR, 0.34; 95% CI, 0.15-0.77) or entrectinib (HR, 0.48; 95% CI, 0.27-0.88). Results across sensitivity analyses consistently favored taletrectinib versus crizotinib or entrectinib. In a descriptive safety comparison, there were no marked differences in TRAE rates across taletrectinib, crizotinib, and entrectinib. In this analysis, taletrectinib was associated with more favorable response and survival outcomes compared with crizotinib or entrectinib in TKI-naïve patients with ROS1+ NSCLC after adjustment for baseline characteristics, supporting taletrectinib as an effective treatment option in this patient population.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 5.3
- 新锐分区
- 2区