Real-world treatment sequencing and survival in ROS1-Rearranged NSCLC across evolving treatment eras: Findings from the AURORA multi-centre registry (AURORA-ROS1).
Summary
This Australian multicenter study, derived from the AURORA registry, analyzed real-world treatment sequencing and survival in 115 patients with ROS1-rearranged NSCLC between 2012 and 2025. It revealed that a majority of patients (74%) received a ROS1 inhibitor as first-line therapy, with increasing use of later-generation inhibitors. Median overall survival was 56 months, extending to 80 months for those treated with a later-generation ROS1 inhibitor in the first line. Brain metastases and high PD-L1 expression were associated with shorter overall survival.
Analysis
This multicenter real-world cohort study provides valuable data on the longitudinal management of ROS1-rearranged NSCLC, highlighting the significant impact of ROS1 inhibitors. The findings suggest a substantial clinical benefit from later-generation ROS1 inhibitors in the first line, with a median progression-free survival of 48 months compared to 17 months for earlier generations, although the difference did not reach statistical significance (p=0.071). The median overall survival of 80 months with first-line later-generation ROS1 inhibitors is particularly encouraging and could warrant confirmatory clinical trials or a re-evaluation of treatment guidelines. The study also identifies important prognostic factors, such as the presence of brain metastases and PD-L1 status ≥ 50%, which are associated with significantly reduced overall survival, suggesting the need for tailored therapeutic approaches for these subgroups. Access to reflex molecular testing and clinical trial enrollment appears to be a key driver of the favorable survival observed, reinforcing the importance of these practices for improving clinical outcomes in the short to medium term (1-3 years).