Real-world data on the use and outcomes of crizotinib in ROS1-rearranged non-small-cell lung cancer (NSCLC) are limited. This study aims to analyze the real-world efficacy of crizotinib in South Korea and explore the utilization of liquid biopsies that implement next-generation sequencing (NGS) using cell-free total nucleic acids. In this prospective multicenter cohort study, 40 patients with ROS1-rearranged NSCLC, either starting or already on crizotinib, were enrolled. Patients had a median age of 61 years, with 32.5% presenting brain/central nervous system (CNS) metastases at treatment initiation. At the data cutoff, 48.0% were still in treatment; four continued with it even after disease progression due to the clinical benefits. The objective response rate was 70.0%, with a median duration of response of 27.8 months. The median progression-free survival was 24.1 months, while the median overall survival was not reached. Adverse events occurred in 90.0% of patients, primarily with elevated transaminases, yet these were mostly manageable. The NGS assay detected a CD74–ROS1 fusion in 2 of the 14 patients at treatment initiation and identified emerging mutations, such as ROS1 G2032R, ROS1 D2033N, and KRAS G12D, during disease progression. These findings confirm crizotinib’s sustained clinical efficacy and safety in a real-world context, which was characterized by a higher elderly population and higher rates of brain/CNS metastases. The study highlights the clinical relevance of liquid biopsy for detecting resistance mechanisms, suggesting its value in personalized treatment strategies.
关于克唑替尼在ROS1重排非小细胞肺癌（NSCLC）临床应用及疗效的真实世界数据较为有限。本研究旨在分析克唑替尼在韩国的真实世界疗效，并探索基于游离总核酸进行二代测序（NGS）的液体活检技术的应用情况。在这项前瞻性多中心队列研究中，共纳入40例正在启动或已接受克唑替尼治疗的ROS1重排NSCLC患者。患者中位年龄为61岁，其中32.5%在治疗开始时存在脑/中枢神经系统（CNS）转移。截至数据截止时，48.0%的患者仍在接受治疗；其中4例患者即使出现疾病进展，因持续获得临床获益仍继续用药。客观缓解率为70.0%，中位缓解持续时间为27.8个月。中位无进展生存期为24.1个月，中位总生存期尚未达到。90.0%的患者出现不良事件，主要表现为转氨酶升高，但多数可控。NGS检测在治疗初期的14例患者中发现2例存在CD74–ROS1融合，并在疾病进展期间识别出ROS1 G2032R、ROS1 D2033N及KRAS G12D等新发突变。这些结果证实了克唑替尼在真实世界环境中（以高龄患者比例较高、脑/CNS转移率较高为特征）具有持续的临床疗效与安全性。本研究凸显了液体活检在识别耐药机制方面的临床价值，提示其在个体化治疗策略中具有重要应用前景。
Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer
肿瘤(癌症)患者之家