Real-world data on the treatment of patients with ROS1-positive non-small cell lung cancer.

e20685 Background: ROS1 rearrangements, present in 1–2% of non-small cell lung cancer (NSCLC) cases, are targetable by ALK inhibitors due to the structural similarities between ROS1 and ALK. This study evaluates the real-world effectiveness of ALK inhibitors in treating patients with ROS1-positive NSCLC. Methods: We conducted a retrospective analysis of patients diagnosed with ROS1-positive NSCLC and treated with ALK inhibitors in Moscow from 2019 to 2024. Data on progression-free survival (PFS), overall survival (OS), treatment response, clinicopathologic characteristics, and factors influencing outcomes were collected. Survival outcomes were analyzed using Kaplan-Meier curves, with Log Rank tests and Cox regression used for statistical comparisons and hazard ratio (HR) calculations. Results: The study included 107 patients: 61.7% female and 75% never-smokers. A high proportion (78.1%) had metastatic disease at diagnosis, with lungs (54.7%), bones (29.2%), and brain (21.7%) as common metastatic sites. Crizotinib was the predominant ALK inhibitor used, administered as first-line therapy in 70.8% of cases. At a median follow-up of 31 months, the median OS was 56 months, with a 5-year OS rate of 36% (95% CI: 27.9–45.2). Median PFS was 15 months (95% CI: 4.8–25.2), with a 5-year PFS rate of 23% (95% CI: 16.3–30.2). Therapy response rates included complete response (5.0%), partial response (26.7%), stable disease (57.4%), and progressive disease (10.9%). No significant survival differences were observed between PD-L1-positive and PD-L1-negative patients. Conclusions: This study represents the most extensive real-world analysis from Russia on the treatment of ROS1-positive NSCLC with ALK inhibitors, particularly crizotinib. It confirms favorable progression-free survival (PFS) and overall survival (OS) outcomes comparable to those observed in registration trials. The results reinforce the crucial role of genomic profiling in NSCLC for personalized treatment approaches. Further research is recommended to enhance outcomes for patients with brain metastases or suboptimal initial responses to therapy.