Clinical Progression Modes of Crizotinib Failure and Subsequent Management of Advanced Non‐Small Cell Lung Cancer With ROS 1 Rearrangement

Background Crizotinib is the classic first‐line treatment for ROS 1‐rearranged NSCLC. However, data on the clinical progression modes and recommended options for subsequent treatments after crizotinib treatment failure are limited. Methods Twenty‐eight patients were categorized into dramatic or gradual/local progression groups. We analyzed the clinical characteristics, survival outcomes, and potential resistance mechanisms in different progression modes. Results The median progression‐free survival (mPFS) in the dramatic and gradual/local progression groups was 8.0 and 22.0 months, respectively ( p < 0.001). The median overall survival (mOS) was 14.2 and 90.3 months in the dramatic progression and gradual/local progression groups, respectively ( p < 0.001). Among patients with dramatic progression after crizotinib failure, significant differences were shown in median post‐progression overall survival (mpOS) (7.1 vs. 3.6 vs. 1.0 months, p = 0.037) and mOS (23.1 vs. 18.3 vs. 10.6 months, p = 0.002) across subsequent chemotherapy, targeted therapy, or best supportive care (BSC). ROS 1 kinase domain point mutations were detected predominantly in the dramatic progression group, while the activation of bypass and downstream pathways occurred in the gradual/local progression group. Conclusion The progression modes of ROS 1 rearrangement may predict survival benefits and provide subsequent treatment strategies in ROS 1‐rearranged NSCLC.