ROS1 mutations, which confer sensitivity to crizotinib, are detected in 1% to 2% of NSCLC cases. Previous study showed that, among patients with ROS1-positive disease, crizotinib delays disease progression for a median of about 19 months, after which treatment resistance evolves.
For this study, researchers attempted to distinguish metastasis distribution among ROS1-positive patients from that among ALK-positive patients, given that ALK mutations also confer sensitivity to crizotinib. The researchers also analyzed disease samples taken at different time points from ROS1-positive patients to determine possible mechanisms of crizotinib resistance.
Thirty-nine patients with ROS1 rearrangements and 196 patients with ALK rearrangements were identified; the median ages were 50 and 51, respectively, 72% and 69% were never-smokers, respectively, and 85% and 84% of patients were diagnosed with stage IV disease, respectively.
Compared with ALK-positive patients, participants with ROS1 rearrangements were less likely to present with extrathoracic (59% vs 83.2%) and brain (19.4% vs 39.1%) metastases. At 5 years post-diagnosis this discrepancy continued, with 34% of ROS1-positive patients developing brain metastases vs 73% of ALK-positive patients.
Despite these findings, patients with ALK-positive disease had a non-significantly longer median overall survival (3 vs 2.5 years; P = .786.)
After disease progression during crizotinib therapy, biopsy analyses detected ROS1 resistance mutations in 53% of samples, the most common of which was G2032R (41%).
The authors concluded that “efforts to identify and validate mechanisms of resistance to crizotinib among larger cohorts of patients with ROS1-positive NSCLC are needed.”
Gainor JF, Tseng D, Yoda S, et al. Patterns of metastatic spread and mechanisms of resistance to crizotinib in ROS1-positive non–small-cell lung cancer [published online August 16, 2017]. JCO Precis Oncol. doi:10.1200/PO.17.00063
This article originally appeared on Cancer Therapy Advisor