A Real-World Study: Therapeutic Outcomes of ROS1-Positive Advanced NSCLC.

Background: ROS1 gene rearrangement is an important target for NSCLC treatment. There is not yet sufficient real-world data on ROS1 diagnostic methods, treatment selection, and clinical outcomes in the Chinese population.

Methods: A single-center retrospective collection of patients with a diagnosis of ROS1-positive advanced NSCLC from July 2011 to November 2021 was performed to document the method of ROS1 testing, treatment options, efficacy, and resistance to ROS1 inhibitors in these patients.

Results: The method of ROS1 testing and initial treatment selection were significantly correlated with time. ROS1 testing shifted from FISH (67% pre-2019) to NGS (96.3% post-2019; p < 0.001). First-line ROS1-TKI use increased from 60.0% to 92.0% (p = 0.041). The vast majority of patients (90.0%) chose crizotinib as the initial ROS1 inhibitor, with objective response rates (for patients with target lesions) and median progression-free survival of 82.8% (95% CI: 68.1%-97.9%) and 18.7 months (95% CI: 8.9-28.4 months), respectively. CNS was the most common site of progression for crizotinib (60%, 13/26, including 11 intracranial progressions alone). Compared to patients who received a chemotherapy-based regimen (n = 8) as first-line therapy, patients who received ROS1-TKI (n = 32) as first-line therapy had significantly longer median PFS (18.3 months vs. 3.7 months, p < 0.001). For ROS1 inhibitor-resistant patients, 48.3% of patients underwent rebiopsy throughout the course of their disease, with G2032R being the most common secondary ROS1 mutation (7/8).

Conclusion: With the innovation of diagnostic and therapeutic methods and the expansion of the scope of the health insurance coverage, more and more patients are benefiting from new technologies and targeted drugs. Although crizotinib has brought excellent therapeutic data for ROS1-positive patients, better brain protection strategies should be explored for ROS1-positive patients in the future. In addition, the low rate of rebiopsy in real-world ROS1-positive patients should also be emphasized in clinical practice.