Survival of patients with advanced non-small cell lung cancer harboring different ROS1 fusion subtypes: a real-world study

Abstract Background c-ros oncogene 1 (ROS1) rearrangement is a rare yet significant genetic abnormality in non-small cell lung cancer. However, real-world treatment data for Non-Small Cell Lung Cancer (NSCLC) patients with different ROS1 fusion subtypes remain limited. Methods Medical records of 99 NSCLC patients with ROS1 rearrangement diagnosed at Beijing Chest Hospital from February 2017 to January 2025 were reviewed. Clinicopathological characteristics, treatment regimens, and efficacy were retrospectively collected, and factors influencing therapeutic outcomes were analyzed. Results A total of 55 patients were included in this study. CD74 was the most common fusion partner. Targeted therapy accounts for 87.3% of first-line treatment. All patients received targeted therapy during their treatment course. The objective response rate (ORR) for first-line treatment was 72.7%, with a median progression-free survival (PFS) of 18.9 months. SDC4 subtype group showed significantly lower ORR than non-SDC4 subtype group in first-line treatment (44.4% vs. 86.1%, P = 0.025). Patients with programmed death-ligand 1 (PD-L1) < 1% had remarkably longer median PFS compared to those with PD-L1 ≥ 1% (not reached vs. 17.3 months, P = 0.031). Univariate Cox regression analysis revealed that SDC4 subtype and baseline bone metastasis were associated with significantly shorter median PFS (7.5 months vs. 22.4 months, P = 0.026; 7.5 months vs. 24.2 months, P = 0.009, respectively). In addition, patients received first-line targeted therapy and those responded to first-line treatment showed noticeably longer median PFS (22.4 months vs. 6.4 months, P = 0.005; 23.6 months vs. 4.4 months, P < 0.001, respectively). Multivariate analysis revealed that SDC4 subtype, bone metastasis status, and the use of TKIs as first-line treatment were independent prognostic factors for PFS of first-line therapy. The median overall survival (OS) of the total patients was 59.8 months. Univariate Cox regression analysis showed that smoking history and baseline liver metastasis were associated with a remarkably shorter median OS (22.6 months vs. 63.2 months, P = 0.018; and 23.8 months vs. 63.2 months, P = 0.013, respectively), while response to the initial targeted therapy was related to significantly longer median OS (59.8 months vs. 22.6 months, P = 0.043). Conclusions Patients with advanced ROS1-rearranged NSCLC benefit from targeted therapy. SDC4 subtype, PD-L1 expression level and baseline metastasis status affects efficacy and survival.