Different Types of ROS1 Fusion Partners Yield Comparable Efficacy to Crizotinib

Abstract

ROS1 rearrangements define a distinct molecular subset of non-small-cell lung cancer (NSCLC), which can be treated effectively with crizotinib, a tyrosine kinase inhibitor (TKI) targeting ROS1/MET/ALK rearrangements. Diverse efficacy was observed in ROS1-rearranged NSCLC patients. Because of its rareness, very limited studies have investigated the correlation between different fusion partners and response to crizotinib. In this study, we retrospectively screened 6,235 advanced NSCLC patients (stage IIIB to IV) from five hospitals and identified 106 patients with ROS1 rearrangements based on either plasma or tumor tissue testing using capture-based targeted sequencing. The most frequently occurring fusion partners included cluster of differentiation 74 (CD74), ezrin (EZR), syndecan 4 (SDC4), and tropomyosin 3 (TPM3), occurring in 49.1%, 17%, 14.2%, and 4.7% of patients, respectively. Among them, 38 patients were treated with crizotinib. Seventeen patients were treatment naive, and the remaining were previously treated with pemetrexed-based chemotherapy. Collectively, there was no significant difference among patients with various types of ROS1 fusion partners in overall survival (OS) and progression-free survival (PFS). Patients who were treated with crizotinib as first-line therapy showed comparable PFS (p = 0.26) to patients who were previously treated with pemetrexed-based chemotherapy. For treatment-naive patients, patients with low baseline ROS1 allelic fraction (AF) had a statistically significant longer OS than those with high ROS1 AF (184 vs. 110 days, p = 0.048). Collectively, our study demonstrates that ROS1+ patients with various fusion partners show comparable efficacy to crizotinib.