Phase II trial of everolimus with sorafenib for patients with differentiated thyroid cancer (DTC) who progress on sorafenib alone.
2010
TPS263 Background: Several trials have shown the activity of multikinase inhibitors in the treatment of iodine-refractory differentiated thyroid cancer. Phase II trials at our institution and others demonstrated that sorafenib has significant clinical activity. Radiographically, resistance often occurs in a subset of sites. Using immunohistochemistry (IHC) on progressing nodules we have observed subregions of tumor cells that express higher levels of p-AKT and p-S6 (downstream of mTOR). Finally, discontinuation of sorafenib can lead to an increase in the progression rate due to the resumption of growth of previously responsive nodules. Taken together, these data argue for the continuation of sorafenib while adding additional therapeutic agents to target the progressing clone of cells. This use of “intelligent design” has led us to open a phase II trial in which we add everolimus, which targets mTOR activity, to sorafenib in patients at the time of progression on sorafenib alone. Methods: Thirty-five patie...
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