Department of Oncology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.
Alberta Precision Laboratories, Molecular Pathology Laboratory, 3535 Research Road NW, Calgary, AB T2L 2K8, Canada.
Curr Oncol. 2022 Mar 14;29(3):1967-1982. doi: 10.3390/curroncol29030160.
The use, safety and effectiveness of crizotinib as part of the management of ROS1-rearranged NSCLC patients in a real-world Canadian clinical cohort was the focus of this retrospective review. Twenty-one ROS1-rearranged patients with advanced/metastatic disease receiving crizotinib between 2014-2020 were identified; crizotinib demonstrated tolerability and effectiveness in this population where outcomes were similar to those described in other crizotinib-treated real-world cohorts, but lower than those of the PROFILE 1001 clinical trial population. Systemic anti-cancer therapy prior to crizotinib initiation occurred in half of the study cohort, with platin-pemetrexed and immune checkpoint inhibitors being most common. Platin-pemetrexed showed good effectiveness in this cohort, but despite high prevalence of upregulated PD-L1 expression, immune checkpoint inhibitors showed poor effectiveness in his cohort. Among all systemic therapies received, crizotinib showed the most effective disease control, although longer intervals between diagnosis and crizotinib initiation were more common among those showing a lack of clinical response to crizotinib, and patients with brain metastases at the time of crizotinib initiation also showed increased diagnosis to crizotinib initiation intervals and decreased clinical response to crizotinib. This study reveals crizotinib has clinical benefit, but timely identification of ROS1-rearrangements and initiation targeted therapies appears important to maximize outcome in this population.
克唑替尼在真实世界加拿大临床队列中作为 ROS1 重排 NSCLC 患者管理的一部分的使用、安全性和有效性是本回顾性研究的重点。在 2014-2020 年间，确定了 21 名接受克唑替尼治疗的晚期/转移性 ROS1 重排患者；在该人群中，克唑替尼具有耐受性和有效性，其结果与其他接受克唑替尼治疗的真实世界队列相似，但低于 PROFILE 1001 临床试验人群。在开始使用克唑替尼之前，有一半的研究队列接受了全身性抗癌治疗，其中铂类培美曲塞和免疫检查点抑制剂最为常见。在本队列中，铂类培美曲塞显示出良好的疗效，但尽管 PD-L1 表达上调的比例很高，免疫检查点抑制剂在本队列中的疗效仍不佳。在所有接受的全身性治疗中，克唑替尼显示出最有效的疾病控制效果，尽管那些对克唑替尼缺乏临床反应的患者中，诊断和开始使用克唑替尼之间的时间间隔较长，而且在开始使用克唑替尼时已有脑转移的患者中，诊断和开始使用克唑替尼之间的时间间隔也较长，对克唑替尼的临床反应也降低。本研究表明克唑替尼具有临床获益，但及时识别 ROS1 重排并启动靶向治疗对于最大化该人群的治疗效果似乎很重要。
