Efficacy of Crizotinib among Different Types of ROS1 Fusion Partners in Patients with ROS1-Rearranged Non-Small Cell Lung Cancer
Efficacy of Crizotinib among Different Types of ROS1 Fusion Partners in Patients with ROS1-Rearranged Non-Small Cell Lung Cancer
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DOI：
10.1016/j.jtho.2018.04.016
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发表时间：
2018-07-01
影响因子：
20.4
通讯作者：
Lu, Shun
中科院分区：
文献类型：
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作者：
Li, Ziming;Shen, Lan;Lu, Shun
简介：使用间变性淋巴瘤激酶/ROS 1/间质-上皮转化因子抑制剂（如克唑替尼）可有效治疗ROS 1再表达阳性NSCLC;然而，缓解率仍存在差异。虽然已经确定了几个ROS 1融合伴侣，克唑替尼在不同类型的ROS 1融合partners.Methods患者的疗效知之甚少：我们回顾了2014年4月至2016年12月在我们的机构接受克唑替尼治疗的ROS 1重排患者的临床病理数据。通过桑格测序法对肿瘤组织进行ROS 1基因重排的检测。结果：在本研究中，共检测到49例ROS 1基因重排的患者，均接受了克唑替尼治疗。可获得36例患者的肿瘤标本，其中19例被发现具有CD 74分子基因（CD 74）-ROS 1融合伴侣。在治疗前，发现CD 74-ROS 1组的脑转移率较高（6比0 [p = 0.020]）。所有患者中克唑替尼的客观缓解率为83.3%，而非CD 74-ROS 1和CD 74-ROS 1组分别为94.11%和73.68%。与CD 74-ROS 1组相比，非CD 74-ROS 1组的无进展生存期显著延长（17.63个月vs 12.63个月[p = 0.048]），总生存期显著延长（44.50个月vs 24.33个月[p = 0.036]）。在多变量分析中，与总生存率相关的唯一因素是治疗前存在脑转移（p = 0.010）。有没有显着的因素与无进展生存的多变量analysis.Conclusions：这些研究结果表明，患者与CD 74-ROS 1融合的合作伙伴更容易出现脑转移。虽然没有独立意义，但在非CD 74-ROS 1组患者中观察到克唑替尼治疗后生存期改善的趋势。(C)2018年国际肺癌研究协会。爱思唯尔公司出版All rights reserved.
Introduction: ROS1 rearrangement-positive NSCLC can be treated effectively with an anaplastic lymphoma kinase/ROS1/mesenchymal-epithelial transition factor inhibitor such as crizotinib; however, the rate of response remains variable. Although several ROS1 fusion partners have been identified, the efficacy of crizotinib in patients with different types of ROS1 fusion partners is poorly understood.Methods: We reviewed clinicopathological data of patients with ROS1 rearrangement who received crizotinib therapy at our institution between April 2014 and December 2016. ROS1 fusion partners were evaluated by using Sanger sequencing for available tumor tissue.Results: During the study, 49 patients were found to have ROS1 rearrangement and were subsequently treated with crizotinib. Tumor specimens were available for 36 patients, of whom 19 were found to have CD 74molecule gene (CD74)-ROS1 fusion partners. Before therapy, those in the CD74-ROS1 group were found to have a higher rate of brain metastases (six versus 0 [p = 0.020]). The objective response rate for crizotinib was 83.3% in all patients, whereas it was 94.11% and 73.68% in the non-CD74-ROS1 and CD74-ROS1 groups, respectively. As compared with the CD74-ROS1 group, the non-CD74-ROS1 group had both a significantly longer progression-free survival (17.63 months versus 12.63 months [p = 0.048]) and a significantly longer overall survival (44.50 months versus 24.33 months [p = 0.036]). On multivariable analysis, the only factor associated with overall survival was presence of brain metastases before therapy (p = 0.010). There were no significant factors associated with progression-free survival in the multivariable analysis.Conclusions: These findings suggests that patients with CD74-ROS1 fusion partners are more likely to present with brain metastases. Although not independently significant, a trend toward improved survival was observed in patients in the non-CD74-ROS1 group when they were treated with crizotinib. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.