Clinical Treatment Patterns, Molecular Characteristics and Survival Outcomes of ROS1-rearranged Non-Small Cell Lung Cancer: A Large Multicenter Retrospective Study

Background: Non -small cell lung cancer (NSCLC) harboring ROS1 rearrangements is a molecular subset that exhibits favorable responses to tyrosine kinase inhibitor (TKI) treatment than chemotherapy. This study investigated real -world treatment patterns and survival outcomes among patients with ROS1-rearranged advanced NSCLC. Methods: We conducted a retrospective analysis of patients with ROS1-rearranged advanced NSCLC treated in four different hospitals in China from August 2018 to March 2022. The study analyzed gene fusion distribution, resistance patterns, and survival outcomes. Results: ROS1 rearrangement occurs in 1.8 % (550/31,225) of our study cohort. CD74 was the most common ROS1 fusion partner, accounting for 45.8 %. Crizotinib was used in 73.9 % of patients in the first -line treatment, and an increased use of chemotherapy, ceritinib, and lorlatinib was seen in the second -line setting. Lung (43.2 %) and brain (27.6 %) were the most common sites of progression in first -line setting, while brain progression (39.2 %) was the most common site of progression in second -line. Median overall survival was 46 months (95 % confidence intervals: 39.6-52.4). First -line crizotinib use yielded significantly superior survival outcomes over chemotherapy in terms of progression -free (18.5 vs. 6.0; p < 0.001) and overall survival (49.8 vs. 37; p = 0.024). The choice of treatment in the latter line also had survival implications, wherein survival outcomes were better when first -line crizotinib was followed by sequential TKI therapy than first -line chemotherapy followed by TKI therapy. Conclusions: Our study provided insights into the real -world treatment, drug resistance patterns, and survival outcomes among patients with ROS1-rearranged NSCLC. This information serves as a valuable reference for guiding the treatment of this molecular subset of NSCLC.