Crizotinib in Patients With ROS1-Positive NSCLC With or Without Brain Metastases: Post Hoc Analysis of Phase II METROS Trial

Introduction: Crizotinib, the first approved targeted therapy for ALK-positive advanced NSCLC, is also indicated for ROS1-rearranged NSCLC. This post hoc analysis of the phase II METROS trial explores long-term survival outcomes with crizotinib, focusing on the impact of baseline brain metastases (BM). Methods: This post hoc analysis of the METROS study assessed survival outcomes in patients with ROS1-rearranged NSCLC, evaluating progression-free survival (PFS), overall survival (OS), and the incidence and severity of adverse events, both in the overall cohort and by baseline BM status. Results: Among 64 patients with ROS1-positive NSCLC with a median follow-up of 54.4 months, median PFS and OS were 13.8 months (95% CI: 7.4-20.2) and 40.5 months (95% CI: 27.9-53.1), respectively. Patients with BM (N = 17) had significantly shorter PFS (6.8 versus 17.4 mo) and OS (16.4 versus 42.8 mo) than those without BM. The safety profile of crizotinib remained consistent with previous reports, with most adverse events being grade 1 or 2 and no new safety concerns identified. Conclusion: This analysis supports the efficacy of crizotinib in patients with advanced NSCLC and ROS1 rearrangements, although its activity in patients with BM remains limited, highlighting the need for brain-penetrant tyrosine kinase inhibitors to improve outcomes in this patient group.