Topal Alper, Akdag Goncagul, Yildirim Sedat, Kinikoglu Oguzcan, Isik Deniz, Yildirim Gizem, Tunbekici Salih, Kus Fatih, Acarbay Aydın, Guliyev Murad, Majidova Nargiz, Kutlu Yasin, Erman Mustafa, Odabas Hatice, Turan Nedim, Karadurmus Nuri
Department of Medical Oncology, Health Science University, Gulhane Research and Training Hospital, Ankara 06010, Turkey.
Department of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Istanbul 34865, Turkey.
Medicina (Kaunas). 2025 Mar 12;61(3):490. doi: 10.3390/medicina61030490.
ROS1 rearrangement is a rare but targetable alteration in non-small-cell lung cancer (NSCLC), occurring in 1-2% of cases. Crizotinib, a tyrosine kinase inhibitor, has demonstrated efficacy in clinical trials, but real-world data remain limited. This study evaluates the safety and efficacy of crizotinib in ROS1-rearranged NSCLC patients in a real-world setting. This multicenter, retrospective research included 43 individuals with advanced/metastatic NSCLC and confirmed ROS1 rearrangements. Patients were treated with crizotinib in first- or second-line settings. Efficacy endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Safety was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The median follow-up was 45.8 months. The ORR for first-line crizotinib was 72.1%, with a DCR of 79%. The median PFS was 20.9 months (95% CI: 6.02-35.69), and the median OS was 52.7 months (95% CI: 13.08-92.31). ECOG performance status was a significant prognostic factor for ORR ( = 0.02). The most common adverse events were fatigue (16.2%), elevated transaminases (13.9%), and vision disorders (11.6%). All reported adverse events were grade 1 or 2, with no grade ≥ 3 events observed. Crizotinib demonstrated significant efficacy and a favorable safety profile in real-world individuals with ROS1-rearranged NSCLC. These findings align with pivotal trials, underscoring crizotinib's role as a standard treatment for this molecular subset. Further prospective studies are warranted to explore intracranial efficacy and long-term outcomes.
ROS1重排在非小细胞肺癌（NSCLC）中是一种罕见但可靶向治疗的改变，发生率为1%-2%。克唑替尼是一种酪氨酸激酶抑制剂，已在临床试验中证明有效，但真实世界的数据仍然有限。本研究评估了克唑替尼在真实世界中对ROS1重排的NSCLC患者的安全性和有效性。这项多中心回顾性研究纳入了43例晚期/转移性NSCLC且确诊为ROS1重排的患者。患者在一线或二线治疗中接受克唑替尼治疗。疗效终点包括无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）和疾病控制率（DCR）。使用不良事件通用术语标准（CTCAE）第5.0版评估安全性。中位随访时间为45.8个月。一线使用克唑替尼的ORR为72.1%，DCR为79%。中位PFS为20.9个月（95%CI：6.02-35.69），中位OS为52.7个月（95%CI：13.08-92.31）。ECOG体能状态是ORR的一个重要预后因素（ = 0.02）。最常见的不良事件是疲劳（16.2%）、转氨酶升高（13.9%）和视力障碍（11.6%）。所有报告的不良事件均为1级或2级，未观察到≥3级事件。克唑替尼在真实世界中ROS1重排的NSCLC患者中显示出显著疗效和良好的安全性。这些发现与关键试验一致，强调了克唑替尼作为该分子亚群标准治疗的作用。有必要进行进一步的前瞻性研究以探索颅内疗效和长期结局。
