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

TLDR

The study aimed to assess whether dabrafenib could induce radioiodine uptake in patients with BRAF V600E‑mutant, iodine‑refractory metastatic papillary thyroid cancer. Ten such patients received dabrafenib 150 mg twice daily for 25 days, followed by a thyrotropin‑stimulated 4 mCi iodine‑131 whole‑body scan; those with new uptake continued dabrafenib for 17 days before receiving 150 mCi iodine‑131. Six of ten patients (60%) showed new radioiodine uptake, and among those treated with high‑dose iodine‑131, two achieved partial responses and four had stable disease at three months, with thyroglobulin decreasing in four of six; dabrafenib was well tolerated aside from one skin carcinoma, supporting its potential as a new therapeutic approach.

Abstract

To determine whether the selective BRAF inhibitor, dabrafenib, can stimulate radioiodine uptake in BRAF V600E-mutated unresectable or metastatic iodine-refractory papillary thyroid cancer (PTC).Ten patients with BRAF 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.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.Dabrafenib can stimulate radioiodine uptake in patients with metastatic BRAF V600E-mutant iodine-refractory PTC, representing a potential new therapeutic approach for these patients.