Clinical Analysis Of ROS1 Fusion Gene In Non-small Cell Lung Cancer

Objective:ROS1 rearrangement is an important therapeutic target that occurs in approximately 1-2% of patients with non-small cell lung cancer(NSCLC).It has been shown that ROS1-rearranged patients could benefit from crizotinib treatment.However,the data on the efficacy of crizotinib in patients with different ROS1 fusion partners is still limited.The efficacy of crizotinib against brain metastases in ROS1-rearranged patients is also poorly understood.Thus,this study is to enrich the clinical data and provide evidence for the personalized clinical practice of NSCLC patients with ROS1 rearrangement in China.Methods:Clinical data of 128 ROS1-rearranged NSCLC patients treated in Shanghai Chest Hospital between August 2010 and December 2017 was collected,including clinicopathological features,incidence of brain metastases,efficacy and tolerability of different treatment regimens.ROS1 fusion partners were detected by using Sanger sequencing.Results:The median age of the patients was 54.5 years,and 60.9% were female.The most of patients(78.9%)were never-smokers.Adenocarcinoma was common(99.2%).Multivariate analysis indicated that N2 metastasis was associated with short disease-free survival in postoperative patients(HR: 3.968,95% CI: 1.047-15.029,P=0.043).Objective response rate(86.7% vs 44.7%,P<0.001)and median PFS(progression-free survival)(18.4 vs 8.6 months,P<0.001)of the advanced patients who received crizotinib as first-line treatment were significantly better than patients treated with pemetrexed-based treatment.CD74-ROS1 fusion was the most common ROS1 fusion partner.The median PFS(12.6 vs 18.9 months,P=0.046)and OS(overall survival)(28.1 vs 54.4 months,P=0.032)of patients in CD74-ROS1 group were shorter than patients in non-CD74-ROS1 group when treated with crizotinib.However,there was no significant difference between the two groups in the multivariate analysis.The incidence of brain metastases was 22.0% at the initial diagnosis.The median PFS(10.4 vs 18.4 months,P=0.022)and OS(18.8 vs 54.4 months,P=0.002)of patients with brain metastases when treated with crizotinib were significantly shorter than patients without brain metastases.There were no significant differences in median intracranial time to progression regardless of local brain treatment(P=0.087).The brain is still the common site of progression during crizotinib treatment.Conclusions:ROS1-rearranged NSCLC patients have distinct clinical features.The efficacy of crizotinib is superior to the chemotherapy in advanced patients.However,the patients in CD74-ROS1 group or with brain metastases have shorter PFS and OS when they received crizotinib treatment.The brain progression is commonly observed during crizotinib treatment.It is important to optimize the therapeutic strategies for ROS1-rearranged NSCLC.Next-generation ROS1 inhibitors are clinically warranted.