Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
J Thorac Oncol. 2018 Jul;13(7):987-995. doi: 10.1016/j.jtho.2018.04.016. Epub 2018 Apr 25.
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.
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.
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 74 molecule 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.
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.
ROS1 重排阳性的非小细胞肺癌可以通过间变性淋巴瘤激酶/ROS1/间质上皮转化因子抑制剂（如克唑替尼）进行有效治疗；然而，反应率仍然各不相同。尽管已经鉴定出几种 ROS1 融合伙伴，但对于不同类型 ROS1 融合伙伴的克唑替尼疗效知之甚少。
我们回顾了 2014 年 4 月至 2016 年 12 月期间在我们机构接受克唑替尼治疗的 ROS1 重排患者的临床病理数据。通过 Sanger 测序评估 ROS1 融合伙伴在可用肿瘤组织中的存在情况。
在研究期间，发现 49 例患者存在 ROS1 重排，并随后接受克唑替尼治疗。36 例患者有肿瘤标本，其中 19 例为 CD74 分子基因（CD74）-ROS1 融合伙伴。在治疗前，CD74-ROS1 组的脑转移发生率更高（6 例与 0 例[P=0.020]）。所有患者对克唑替尼的客观缓解率为 83.3%，而非 CD74-ROS1 组和 CD74-ROS1 组的客观缓解率分别为 94.11%和 73.68%。与 CD74-ROS1 组相比，非 CD74-ROS1 组的无进展生存期（17.63 个月与 12.63 个月[P=0.048]）和总生存期（44.50 个月与 24.33 个月[P=0.036]）均显著延长。多变量分析显示，与总生存期相关的唯一因素是治疗前存在脑转移（P=0.010）。多变量分析中无与无进展生存期相关的显著因素。
这些发现表明，具有 CD74-ROS1 融合伙伴的患者更有可能出现脑转移。尽管无统计学意义，但在接受克唑替尼治疗的非 CD74-ROS1 组患者中，生存有改善的趋势。
