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Gregory J. Riely, MD, PhD

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Are Kinase Inhibitors the Future for Patients With Refractory Thyroid Cancer?

By: Joshua Swore, PhD
Posted: Thursday, November 10, 2022

Exploring the use of kinase inhibitors to induce redifferentiation for patients with thyroid cancer is the subject of a recent article published in Clinical Cancer Research. “Radioactive iodine treatment is an effective treatment for differentiated thyroid cancer; however, many patients are refractory,” said author Maria E. Cabanillas, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues. “Using targeted drugs to reinduce radioactive iodine sensitivity (“redifferentiation therapy”) has long been sought after as the holy grail in endocrine oncology.”

The perspective highlights the history of treatments for thyroid cancer, emphasizing the use of radioactive iodine as the sole systemic and targeted treatment. Historically, just 20% of patients older than age 40 responded, and cures were uncommon. This has been accommodated using kinase inhibitors to allow redifferentiation to occur in patients with thyroid cancers. Several studies have been conducted to better understand the factors necessary for redifferentiation therapy, including kinase inhibitor selection (among agents such as sorafenib, lenvatinib, larotrectinib, entrectinib, selpercatinib, pralsetinib, cabozantinib) and the timing during radioactive iodine treatment.

Next, the authors reported on the most current literature that explores treatment in patients with BRAF V600E–mutated tumors. Patients were treated with the kinase inhibitors dabrafenib and trametinib prior to radioactive iodine. Treatment resulted in 35% of patients achieving redifferentiation, and the drugs were found to be safe.

Finally, the study authors explored the difficulties of performing clinical trials in this patient population. Consolidating the available data can be difficult, they noted, because of varying definitions of refractory state, potency, and type of mutations. Furthermore, the ideal amount of radioactive iodine that should be administered is largely unknown. Some trials will permit macroscopic disease states alone, but radioactive iodine is reportedly best used on micrometastatic disease states. The authors concluded by emphasizing the need for data on long-term overall survival rates and safety of radioactive iodine in this patient population.

Disclosure: For full disclosures of the study authors, visit aacrjournals.org.


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