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Immunotherapy, New Targeted Approaches Explored in Thyroid Cancer

Danielle Bucco
Published: Monday, Oct 30, 2017

Gregory Daniels, MD, PhD
Gregory Daniels, MD, PhD
As with other solid tumors, researchers are now exploring both BRAF/MEK inhibitor combinations and PD-1 therapy in the field of thyroid cancer for patients who are refractory to radioactive-iodine treatment, according to Gregory Daniels, MD, PhD, who adds that there is an increased emphasis on genetic testing to determine potential driver mutations in these patients.

on Head and Neck Squamous Cell Carcinoma and Thyroid Cancer, Daniels, a clinical professor in the Department of Medicine at University of California, San Diego, discussed the current treatment landscape of thyroid cancer and the development of immunotherapy for patients with this disease.

OncLive: Please provide an overview of your presentation on thyroid cancer.

Daniels: I discussed advanced thyroid cancer, meaning thyroid cancers that have become refractory—usually to radioactive iodine or other conventional therapies, such as surgery. Surgery remains to be the first choice of treatment. However, patients with advanced cancer see their cancer spread to the lungs, bone, or other organs. The main focus of my talk was the current role of medical oncology in the field of thyroid cancers after radioactive-iodine therapy.

What have been some recent advancements in the field?

Like other areas of oncology, thyroid cancer is now getting personalized therapies [targeted to the driver mutations], as well as immunotherapy with checkpoint inhibitors. The 2 FDA-approved medications in thyroid cancer, sorafenib and lenvatinib, are tyrosine kinase inhibitors (TKIs) and target VEGF 1/2/3. That's what is currently happening regarding the genetics for these patients.

Are there any clinical trials in this space that you are excited about?

When looking at a differentiated thyroid cancer—papillary thyroid cancer being the most common—that is refractory to radioactive-iodine therapy and need systemic treatments, the first thing we will do is sequence their somatic mutations in their tumor. That is not whole-genome sequencing, but it is looking at 200 or 300 targets. Thyroid cancer often has the MAP kinase pathway perturbed with a BRAF or RAS mutation in the MAP kinase pathway.

A study that is ongoing is utilizing a MEK inhibitor compared with placebo in patients who have received radioactive iodine. We are looking to give them another dose, but can we enhance the benefit of radioactive iodine by turning off this MAP kinase pathway? We hope to find the answer in that exciting trial.

If drugs such as dabrafenib are approved by the FDA, what impact would they have on the treatment landscape? Would they be better used in combinations?

In my opinion, we should use genetics to discover what is driving the mutation. The next thing that happens with these targeted therapies is resistance. We are beginning to understand these secondary pathways that are coming up. For example, HER3 is activated at MAP kinase resistance when you start turning off BRAF. There are ongoing studies looking at those combinations. 

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TitleExpiration DateCME Credits
Medical Crossfire®: How Can We Optimize Outcomes in Head and Neck Cancers with Immunotherapeutic Strategies?Oct 31, 20191.5
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