RET fusion–positive non-small cell lung cancer in Sweden: a nationwide registry study

BACKGROUND: Rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) is a rare but clinically meaningful molecular subgroup. RET inhibitors have demonstrated marked clinical activity; however, real-world data on disease characteristics and outcomes before their widespread introduction remain limited. This study characterizes clinical features, treatment patterns, and survival outcomes of RET fusion-positive NSCLC in a nationwide Swedish cohort, with other driver subgroups as descriptive comparisons. METHODS: Patients ≥18 years diagnosed with histologically confirmed NSCLC in 2018-2022, registered in the Swedish National Lung Cancer Registry and with next-generation sequencing results available, were included. Individuals were categorized by oncogenic driver status, including RET, ALK, BRAF, EGFR, KRAS, ROS1, or wild type. Progression-free survival (PFS) and overall survival (OS) from diagnosis were estimated using Kaplan-Meier methods and standardized Cox proportional hazards models adjusted for age, sex, performance status, smoking, stage, and histology. RESULTS: A total of 68 patients had RET fusion-positive NSCLC. The RET cohort was characterized by younger age, a high proportion of never-smokers (59%), and predominantly adenocarcinoma histology (96%). Most had stage IV disease at diagnosis and the highest rate of liver metastases (56%). KIF5B-RET (71%) and CCDC6-RET (19%) were the most frequent fusion partners. Adjusted median OS was 28 months (95% confidence interval [CI]: 13-46) for RET, 39 months (95% CI: 29-52) for ALK, and 17-26 months for the other groups, with overlapping CIs. CONCLUSION: RET fusion-positive patients were typically younger never-smokers with adenocarcinoma and had encouraging OS, despite limited access to selective RET inhibitors during the study period.