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.