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

Abstract

<i>RET</i> fusions are oncogenic drivers across different solid tumors. However, the genomic landscape and natural history of patients with <i>RET</i> fusion-positive solid tumors are not well known. We describe the clinical characteristics of RET tyrosine kinase inhibitor (TKI)-naïve patients with <i>RET</i> fusion-positive solid tumors (excluding non-small-cell lung cancer [NSCLC]), treated in a real-world setting and assess the prognostic effect of <i>RET</i> fusions. 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 <i>RET</i> fusion-positive tumors versus matched patients with <i>RET</i> wild-type (<i>RET</i>-WT) tumors. Patients with <i>RET</i>-WT solid tumors were matched (4:1) to patients with <i>RET</i> fusion-positive tumors on the basis of preselected covariates. The study population included 26 patients in the <i>RET</i> fusion-positive cohort, 7,220 patients in the <i>RET-</i>WT cohort (before matching), and 104 patients in the matched <i>RET</i>-WT cohort. Co-occurring genomic alterations were rare in the <i>RET</i> fusion-positive cohort. Median OS was consistently lower in patients with <i>RET</i> fusion-positive tumors versus those with <i>RET</i>-WT tumors, using three different analyses (hazard ratios, 2.0, 1.7, and 2.2). These data suggest that <i>RET</i> 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.