Data from Redifferentiation of Iodine-Refractory <i>BRAF</i> V600E-Mutant Metastatic Papillary Thyroid Cancer with Dabrafenib

Abstract

<div>Abstract<p><b>Purpose:</b> To determine whether the selective BRAF inhibitor, dabrafenib, can stimulate radioiodine uptake in <i>BRAF</i> V600E-mutated unresectable or metastatic iodine-refractory papillary thyroid cancer (PTC).</p><p><b>Experimental Design:</b> Ten patients with <i>BRAF</i> V600E-mutant iodine-refractory PTC were enrolled. Absence of radioiodine uptake on iodine-131 whole body scan obtained within 14 months of study entry was required. Each patient received dabrafenib (150 mg twice daily) for 25 days before thyrotropin α-stimulated iodine-131 whole body scan (4 mCi/148 MBq). Patients whose scan showed new sites of radioiodine uptake remained on dabrafenib for 17 more days, and then were treated with 150 mCi (5.5 GBq) iodine-131. The primary endpoint of the study was the percentage of patients with new radioiodine uptake after treatment with dabrafenib.</p><p><b>Results:</b> Six of 10 patients (60%) demonstrated new radioiodine uptake on whole body scan after treatment with dabrafenib. All 6 were treated with 5.5 GBq iodine-131. Two patients had partial responses and 4 patients had stable disease on standard radiographic restaging at 3 months. Thyroglobulin decreased in 4 of 6 treated patients. One patient developed squamous cell carcinoma of the skin. There were no other significant adverse events attributed to dabrafenib.</p><p><b>Conclusions:</b> Dabrafenib can stimulate radioiodine uptake in patients with metastatic <i>BRAF</i> V600E-mutant iodine-refractory PTC, representing a potential new therapeutic approach for these patients. <i>Clin Cancer Res; 21(5); 1028–35. ©2014 AACR</i>.</p></div>