Characteristics and Survival Outcomes of Patients With Metastatic RET Fusion–Positive Solid Tumors Receiving Non-RET Inhibitor Standards of Care in a Real-World Setting

Abstract

PURPOSE RET fusions are oncogenic drivers across different solid tumors. However, the genomic landscape and natural history of patients with RET fusion–positive solid tumors are not well known. We describe the clinical characteristics of RET tyrosine kinase inhibitor (TKI)-naïve patients with RET fusion–positive solid tumors (excluding non–small-cell lung cancer [NSCLC]), treated in a real-world setting and assess the prognostic effect of RET fusions. METHODS Data for RET TKI-naïve patients with metastatic solid tumors (excluding NSCLC) who had ≥one Foundation Medicine comprehensive genomic profiling test (January 1, 2011-March 31, 2022) were obtained from a deidentified nationwide (US-based) clinicogenomic database. The primary objective of this study was to compare the overall survival (OS) of patients with RET fusion–positive tumors versus matched patients with RET wild-type ( RET-WT) tumors. Patients with RET-WT solid tumors were matched (4:1) to patients with RET fusion–positive tumors on the basis of preselected covariates. RESULTS The study population included 26 patients in the RET fusion–positive cohort, 7,220 patients in the RET-WT cohort (before matching), and 104 patients in the matched RET-WT cohort. Co-occurring genomic alterations were rare in the RET fusion–positive cohort. Median OS was consistently lower in patients with RET fusion–positive tumors versus those with RET-WT tumors, using three different analyses (hazard ratios, 2.0, 1.7, and 2.2). CONCLUSION These data suggest that RET fusions represent a negative prognostic factor in patients with metastatic solid tumors and highlight the need for wider genomic testing and use of RET-specific TKIs that could improve patient outcomes. Our study also highlights the value of real-world data when studying rare cancers or cancers with rare genomic alterations.