Impact of molecular therapy on radioactive iodine uptake in patients with oncogene-driven metastatic differentiated thyroid cancer.

TPS10078 Background: Targetable kinase fusions and mutations are common in pediatric and young adult patients with papillary thyroid cancer (TC) and are associated with metastatic disease and lack of response to radioactive iodine therapy (RAI). While survival outcomes are excellent, less than 20% of children with metastatic TC achieve a complete response to standard treatment with surgery and radioactive iodine (RAI). Thus, repeated RAI therapy is common, increasing the risk of pulmonary fibrosis and secondary malignancies. Targeted kinase inhibitors are highly effective at shrinking oncogene-driven TC. Preliminary data suggest that these targeted therapies can improve tumor differentiation and RAI sensitivity. However, optimal integration of targeted therapy with standard of care RAI for TC remains uncertain. The objective of this study is to evaluate if targeted inhibitors in patients with metastatic, oncogene-driven differentiated TC will improve or restore tumor RAI uptake and ultimately induce durable clinical responses in patients with metastatic differentiated TC. Methods: Patients with TC lung metastases, both RAI naïve and refractory, with an identified targetable molecular driver (Table) and intent to start oncogene-specific targeted therapy are eligible for this study. Patients who received a prior oncogene-specific targeted therapy are excluded. A RAI-whole body scan (WBS) is performed at baseline and after 4 weeks of targeted therapy. Patients will be followed for up to 5 years to monitor clinical response. Response parameters include structural (CT, WBS, and/or neck US) and biochemical (thyroglobulin, thyroglobulin antibodies) evaluation. The primary endpoint is the change in RAI avidity between baseline and 4 weeks of treatment. This will be calculated as the ratio of RAI uptake in the lungs/disease sites versus the whole body for each subject at each time point. Secondary endpoints include progression free survival and the proportion of patients who achieve a complete response to the combination of targeted therapy and RAI. Five of 32 patients have been enrolled. Clinical trial information: NCT05024929 . Table: see text