Targeted Therapy Combined with Pembrolizumab in Anaplastic Thyroid Cancer: Two Phase II Clinical Trials

Thyroid Cancer
Researcher Headshot
Mark Zafereo, MD, FACS
MD Anderson Cancer Center

Summary:

Anaplastic thyroid cancer (ATC) is a rare thyroid cancer representing less than 2% of all thyroid cancers. However, it is one of the most lethal human malignancies with a historical median survival of 3 months after diagnosis. Recent advances in targeted therapy have significantly improved patient survival and improved quality of life. The BRAFV600E mutation was found to be the most common mutation in ATC, affecting up to 50% of patients. A trial led by MD Anderson assessed dabrafenib/trametinib, which targets the BRAFV600E mutation, in BRAF-mutated ATC. As a result, the drug combination gained FDA approval and the 1-year survival of ATC patients has increased from 20% to 80%. Despite the breakthrough, most patients developed resistance to treatment. Two phase II trials evaluating different drugs will be conducted. The first evaluating if the early addition of an immune checkpoint inhibitor, pembrolizumab, to dabrafenib/trametinib will delay treatment resistance. The second evaluating Lenvatinib, which targets VEGFR, in combination with pembrolizumab as a first-line therapy in patients without BRAF mutations, which represents about 60% of ATC patients.

Trial Registration: ClinicalTrials.gov Identifier: NCT04171622 and NCT04675710

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