Clinical Update on Differentiated Thyroid Cancer - Episode 10
Transcript: Marcia S. Brose, MD, PhD: Historically, thyroid cancer was treated by surgery and radioactive iodine. In 1974, adriamycin was FDA approved. However, it wasn’t very effective, and patients with relapsed or refractory disease were still doing poorly. So from 1974 until the 2000s, patients were treated with palliative care for symptom management. Their disease would eventually progress, and they would die, on average, about 2.5 to 3.5 years after radioactive iodine was no longer effective.
In 2005 or 2006, we had the approval of the first agent, which was sorafenib. That dramatically changed the timing of everything. Patients who were RAI [radioactive iodine] refractory were no longer let go with no therapy. They now had a therapy that was fairly tolerable. If it could not reverse some of the growth of the disease, it certainly stabilized it for a considerable amount of time, which allowed for less symptom issues and better pain management and other things.
For most patients who have relapsed or refractory thyroid cancer, and radioactive iodine is no longer working, we’re going to start to consider other therapies—systemic therapies. At this time, we have 2 approved therapies. We have sorafenib, and we also have lenvatinib. The good thing to know about these therapies is that all patients benefit. So what does molecular testing add? We know that patients with BRAF mutations are going to do better, regardless of whether or not they get the drug. So they’ll do better without it, but they’ll do even better with the drug. So it’s nice to know if they’re BRAF positive.
If they’re RAS positive, we know that they’re more likely to relapse sooner. Why is that good? It won’t change the fact that I’ll use sorafenib and lenvatinib—I’ll use both of them sequentially—but it tells me right away that they’re not likely going to get a long response. I have to monitor them closer because RAS is more likely to be associated with a poorly differentiated phenotype. So for those cases, it’s more of a prognostic role. It’s not actually a therapeutic role. But we also now know from phase II data that BRAF inhibitors work very well. Vemurafenib was first shown a few years ago, and dabrafenib has recently been shown to have activity, just in the last year. So if you know that you have a patient with a BRAF mutation, they have a third option. They’re actually going to have that as an option as well.
Interestingly, we now have these very highly selective RET inhibitors that are being looked at in clinical trials. TRK inhibitors are also under clinical investigation. Both of these are for a very specific subtype. If you have a TRK translocation, larotrectinib and some of the other TRK inhibitors that are also in development might be very good options for these patients because they have a very, very tolerable side-effect profile. RET inhibitors are still under investigation, but again, if the patient happens to have a RET point mutation or translocation, you have another option.
They tend to be somewhat exclusive. You’re not going to have both a BRAF mutation and a RET mutation. Usually you’ll have one or the other. Knowing about those 4 genes can help you plan ahead with treatment. And so, all my patients get studied for point mutations of all of the major cancer genes, as well as get a translocation panel. In some centers that are not part of an academic center, some of the tests, like FoundationOne, actually cover both. And so that’s something that I usually like to know at the beginning. Interestingly, what should you actually test? You don’t usually want to test the beginning nodule. You would test, hopefully, a biopsy from a more recent nodule if one has been obtained. If one is not available, I’ll do the testing on the original surgical specimen.
Transcript Edited for Clarity