Medical Oncology, Santa Maria della Misericordia Hospital, University of Perugia, Piazzale Menghini, Perugia, Italy.
Department of Specialized, Experimental, and Diagnostic Medicine, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, Italy.
Clin Lung Cancer. 2020 Sep;21(5):e478-e487. doi: 10.1016/j.cllc.2020.03.008. Epub 2020 Apr 15.
ROS1 rearrangements define a subset of non-small-cell lung cancers (NSCLCs) that are susceptible to therapeutic ROS1 kinase inhibition. Despite the fact that most patients initially respond to the first-generation ROS1 tyrosine kinase inhibitor (TKI) crizotinib, relapse invariably occurs, and therapeutic options upon disease progression are limited.
We conducted a multicenter study of patients with ROS1-rearranged NSCLC who progressed on ROS1 TKIs and examined the clinical outcomes based on the post-progression treatment approaches.
Among 29 patients with ROS1-rearrangement who received at least 1 ROS1 inhibitor, the median age was 51 years (range, 30-80 years), 70.8% of patients were female, and 68.9% were never-smokers. Upon progression to the first TKI, 11 patients (37.9%) received treatment with TKIs beyond progression. The median second progression-free survival to TKIs in patents treated beyond progression was 5.5 months (95% confidence interval [CI], 4.1-9.1 months), whereas the post-progression survival was 21.0 months (95% CI, 5.5 months-not reached [NR]). Eleven (37.9%) patients received a sequential treatment with lorlatinib ROS1 TKIs following a first generation ROS1 TKI. The overall response rate, median progression-free survival, and median overall survival (OS) to next-generation TKIs were 41.7% (95% CI, 15.2%-72.3%), 12.7 months (95% CI, 8.5 months-NR), and 17.0 months (95% CI, 15.8 months-NR), respectively. Patients treated with sequential ROS1 TKIs had a significantly longer median OS compared with those who were not (NR vs. 16.1 months; hazard ratio, 0.26; 95% CI, 0.10-0.78; P = .017).
In this study, we reported that a subset of patients with ROS1-rearranged NSCLC may benefit from treatment with TKIs beyond progression and that sequential treatment with crizotinib followed by lorlatinib is associated with improved OS in patients with ROS1-rearranged NSCLC.
ROS1 重排定义了非小细胞肺癌（NSCLC）的一个亚组，这些患者对 ROS1 激酶抑制剂的治疗敏感。尽管大多数患者最初对第一代 ROS1 酪氨酸激酶抑制剂（TKI）克唑替尼有反应，但不可避免地会复发，并且疾病进展后的治疗选择有限。
我们对接受 ROS1 TKI 治疗后进展的 ROS1 重排 NSCLC 患者进行了一项多中心研究，并根据疾病进展后的治疗方法检查了临床结果。
在接受至少一种 ROS1 抑制剂治疗的 29 名 ROS1 重排患者中，中位年龄为 51 岁（范围，30-80 岁），70.8%的患者为女性，68.9%为从不吸烟者。在第一代 TKI 进展后，有 11 名患者（37.9%）接受了 TKI 以外的治疗。在接受 TKI 以外治疗的患者中，第二次 TKI 无进展生存期的中位数为 5.5 个月（95%CI，4.1-9.1 个月），而进展后生存时间为 21.0 个月（95%CI，5.5 个月-NR）。11 名（37.9%）患者在第一代 ROS1 TKI 后接受了 lorlatinib ROS1 TKI 的序贯治疗。接受下一代 TKI 治疗的患者的总体反应率、中位无进展生存期和中位总生存期（OS）分别为 41.7%（95%CI，15.2%-72.3%）、12.7 个月（95%CI，8.5 个月-NR）和 17.0 个月（95%CI，15.8 个月-NR）。与未接受序贯 ROS1 TKI 治疗的患者相比，接受序贯 ROS1 TKI 治疗的患者中位 OS 显著延长（NR 与 16.1 个月；风险比，0.26；95%CI，0.10-0.78；P=0.017）。
在这项研究中，我们报告说，ROS1 重排 NSCLC 的一部分患者可能受益于 TKI 以外的治疗，而克唑替尼序贯 lorlatinib 治疗与 ROS1 重排 NSCLC 患者的 OS 改善相关。
