Selumetinib Shown to Reverse Radioiodine Resistance in Some Advanced Thyroid Cancers
The experimental drug selumetinib may allow some patients with advanced thyroid cancer to overcome resistance to radioiodine, the most effective therapy for the disease, according to new research from Memorial Sloan-Kettering Cancer Center.
Published in the February 14 issue of the New England Journal of Medicine, the study offers new hope for patients with a disease that can have a poor prognosis. An estimated 56,000 new cases of thyroid cancer are diagnosed each year in the United States, and that number is on the rise, according to the National Cancer Institute. About 5% of these patients will eventually develop distant metastatic disease, and the 10-year survival rate for patients with metastatic tumors that fail to respond to radioiodine is approximately 10%.
According to James A. Fagin, MD, Memorial Sloan-Kettering’s Endocrinology Service Chief and senior author on the study, many trials have tested strategies for overcoming radioiodine resistance in metastatic thyroid cancers, but none have been successful. Previous studies have shown that a cell’s ability to absorb radioiodine is controlled by the MAPK pathway, so Dr. Fagin and his colleagues examined whether selumetinib, an MAPK inhibitor, could reverse radioiodine resistance by inhibiting the signaling of genetic mutations in this pathway. The approach proved effective, especially in patients with thyroid cancers that contain a mutation in the RAS gene, a component of the MAPK pathway.
“Blocking this key pathway increased the uptake of iodine, making radioiodine treatment potentially effective once again,” said Dr. Fagin, who led this research in cells and in mice.
Study Details
Following a 5-day low-iodine diet, researchers administered selumetinib to 20 patients with radioiodine-resistant thyroid carcinoma. After 4 weeks, patients underwent a diagnostic scan that measured how much radioiodine their tumors would absorb. In eight patients, including all five with an NRAS gene mutation, selumetinib increased iodine uptake enough to allow patients to undergo radioiodine therapy.
Following radioiodine therapy, five patients had confirmed partial responses and three had stable disease. In seven of the eight patients, outcomes remained unchanged during 6 months of follow-up. All eight patients had a decreased level of serum thyroglobulin and none experienced serious side effects from selumetinib.
“An advantage of this therapeutic strategy is that only a short course of drug therapy is required to elicit a significant clinical effect,” Dr. Fagin said, adding that “the initial results show promise for RAS-mutant disease, but the hope is that a larger trial will shed light on whether selumetinib can be effective for a broader range of advanced thyroid cancer subtypes.”
Memorial Sloan-Kettering will lead the international, multicenter phase III clinical trial of selumetinib later this year. The trial, which will be sponsored by AstraZeneca, will enroll patients who have recently had a total thyroidectomy due to thyroid cancer that has spread to nearby tissue or lymph nodes.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
