Analysis of Acquired Fusion Mutations in EGFR-TKIs-Resistant Patients with Advanced Lung Cancer

To determine the characteristics of non-small cell lung cancer (NSCLC) patients with fusion genes emerging after resistance to EGFR-TKIs. This study retrospectively collected 2800 cases of NSCLC with EGFR-sensitive mutations who underwent tissue-based next- generation sequencing (NGS) testing at least once. Patients with acquired fusion mutations, including ALK, ROS1, RET, etc., were included in the study, and clinical data, gene mutation status, treatment strategies, and follow-up were collected. Given the small sample size and exploratory design of this case series (n = 9), the findings were reported descriptively. There were six cases of ALK fusion, two cases of RET fusion, and one case of ROS1 fusion. EGFR abundance decreased in five patients, while EGFR was detected as negative in the other four patients. When fusion mutations emerged, the use of ALK/RET/ROS1-TKIs or EGFR-TKIs combined with fusion-TKIs demonstrated efficacy. The progression-free survival ranged from 5 months to ≥39 months. One patient with acquired fusion gene mutations developed small-cell lung cancer transformation after ALK-TKIs resistance. Key Words: Lung cancer, ALK fusion, RET fusion, ROS1 fusion, EGFR-TKIs-resistance, Targeted therapy.