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Precision Medicine in Differentiated Thyroid Cancer

Insights From: Marcia S. Brose, MD, PhD Abramson Cancer Center; Johannes Smit, MD, PhD Radboud University Nijmegen Medical Center
Published: Friday, Dec 14, 2018



Transcript: 

Eric J. Sherman, MD:
The nice thing about thyroid cancer, especially papillary thyroid cancer, is that targetable mutations exist. Right now, everyone knows about BRAF. It’s the most common mutation, and is something that’s very targetable with BRAF inhibitors. While none of those BRAF inhibitors are FDA approved, it has been shown in phase II studies to be very active in thyroid cancer.

What’s more exciting is that there are some less common mutations that we are able to target. We’re seeing great responses in clinical studies. The LOXO-292 drug was presented at the ASCO [American Society of Clinical Oncology] annual meeting this past summer. In RET fusion papillary thyroid cancers, the drug showed an extremely high response rate. It’s also extremely well tolerated. We’ve seen some great results with that drug, but there are other drugs that specifically target RET that are also very well tolerated and are going to have the exact same activity.

The other thing would be NTRK fusion genes. This is something that is also seen in papillary thyroid cancer. In any patient who does not have a BRAF, RAS, or RET fusion gene, you should check for an NTRK fusion gene. We also see excellent responses with these NTRK inhibitors, and we expect that these NTRK inhibitors will definitely be approved for any tumor that has an NTRK fusion gene. So this is another perfect thing for us to target.

The other things that we know exist are the TSC2 or TSC1 mutations. In a study with everolimus, Dana-Farber [Cancer Institute in Boston, Massachusetts], showed that patients with anaplastic thyroid cancer responded extremely well to single-agent everolimus—a near-complete response. We see the exact same thing in differentiated thyroid cancer, where we’re able to give an mTOR inhibitor, and we’re seeing great activity with fewer side effects than we see with other drugs. So I think we’re seeing more and more targets that we can hit. I think that’s one of the more exciting things in thyroid cancer that is going on right now.

Johannes (Jan) Smit, MD, PhD: At this moment, we do not have proper molecular tests to stratify patients in terms of optimal drug treatment. We do not know what a relationship is between the molecular profile of the cancers of our patients and the optimal drugs for a personalized treatment. I expect that in the coming years we will learn a lot about molecular profiles of patients with metastasized thyroid cancer, and profiling will help us stratify patients for better-targeted treatment. As we have seen in other types of cancer, according to a molecular profile, we choose the optimal drug. At this moment, this is not the case in thyroid cancer. It’s more or less a black box still. However, I expect that this will change in the coming years.


Transcript Edited for Clarity 
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Transcript: 

Eric J. Sherman, MD:
The nice thing about thyroid cancer, especially papillary thyroid cancer, is that targetable mutations exist. Right now, everyone knows about BRAF. It’s the most common mutation, and is something that’s very targetable with BRAF inhibitors. While none of those BRAF inhibitors are FDA approved, it has been shown in phase II studies to be very active in thyroid cancer.

What’s more exciting is that there are some less common mutations that we are able to target. We’re seeing great responses in clinical studies. The LOXO-292 drug was presented at the ASCO [American Society of Clinical Oncology] annual meeting this past summer. In RET fusion papillary thyroid cancers, the drug showed an extremely high response rate. It’s also extremely well tolerated. We’ve seen some great results with that drug, but there are other drugs that specifically target RET that are also very well tolerated and are going to have the exact same activity.

The other thing would be NTRK fusion genes. This is something that is also seen in papillary thyroid cancer. In any patient who does not have a BRAF, RAS, or RET fusion gene, you should check for an NTRK fusion gene. We also see excellent responses with these NTRK inhibitors, and we expect that these NTRK inhibitors will definitely be approved for any tumor that has an NTRK fusion gene. So this is another perfect thing for us to target.

The other things that we know exist are the TSC2 or TSC1 mutations. In a study with everolimus, Dana-Farber [Cancer Institute in Boston, Massachusetts], showed that patients with anaplastic thyroid cancer responded extremely well to single-agent everolimus—a near-complete response. We see the exact same thing in differentiated thyroid cancer, where we’re able to give an mTOR inhibitor, and we’re seeing great activity with fewer side effects than we see with other drugs. So I think we’re seeing more and more targets that we can hit. I think that’s one of the more exciting things in thyroid cancer that is going on right now.

Johannes (Jan) Smit, MD, PhD: At this moment, we do not have proper molecular tests to stratify patients in terms of optimal drug treatment. We do not know what a relationship is between the molecular profile of the cancers of our patients and the optimal drugs for a personalized treatment. I expect that in the coming years we will learn a lot about molecular profiles of patients with metastasized thyroid cancer, and profiling will help us stratify patients for better-targeted treatment. As we have seen in other types of cancer, according to a molecular profile, we choose the optimal drug. At this moment, this is not the case in thyroid cancer. It’s more or less a black box still. However, I expect that this will change in the coming years.


Transcript Edited for Clarity 
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