Redifferentiation of iodine-refractory BRAF V600E-mutant metastatic papillary thyroid cancer with dabrafenib

S. Michael Rothenberg, David G. McFadden, Edwin L. Palmer, Gilbert H. Daniels, Lori J. Wirth

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

Purpose: 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). Experimental Design: Ten patients with BRAF V600E-mutant iodine-refractory PTC were enrolled. Absence of radio-iodine 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. Results: 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. Conclusions: Dabrafenib can stimulate radioiodine uptake in patients with metastatic BRAF V600E-mutant iodine-refractory PTC, representing a potential new therapeutic approach for these patients.

Original languageEnglish (US)
Pages (from-to)1028-1035
Number of pages8
JournalClinical Cancer Research
Volume21
Issue number5
DOIs
StatePublished - Mar 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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