Hackshaw, Allan; Fajardo, Otto; Dafni, Urania; Gelderblom, Hans; Garrido, Pilar; Siena, Salvatore; Taylor, Matthew H; ... Nikolaidis, Christos; + view all Hackshaw, Allan; Fajardo, Otto; Dafni, Urania; Gelderblom, Hans; Garrido, Pilar; Siena, Salvatore; Taylor, Matthew H; Bordogna, Walter; Nikolaidis, Christos; - view fewer (2024) 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. JCO Precision Oncology , 8 (8) , Article e2300334. 10.1200/PO.23.00334.

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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.

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