Efficacy of Crizotinib among Different Types ofROS1 Fusion Partners in Patients with ROS1-Rearranged Non-Small Cell Lung Cancer.

Abstract

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.