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Treating Radioiodine-Refractory DTC After Progression on Lenvatinib


A brief discussion on therapeutic options one may consider after progression on lenvatinib therapy for iodine-refractory DTC.


Lori Wirth, MD: I do want to shift gears, once again, just to touch briefly on what we do when lenvatinib no longer works. For most people, one can have good control of their thyroid cancer over a long period of time with a drug such as lenvatinib [Lenvima], but ultimately, thyroid cancer cells will begin to grow again and become resistant to a first-line therapy such as lenvatinib. Until recently, we didn’t necessarily have great data to guide us, but we do now have data that have recently been published looking at a drug called cabozantinib [Cabometyx] in patients with refractory differentiated thyroid cancer that has progressed after treatment on a multikinase inhibitor. That was the COSMIC-311 trial; that trial randomly assigned patients who had progressed on a drug such as lenvatinib to receive either cabozantinib or placebo. Again, what the COSMIC-311 trial showed was that patients who were randomized to cabozantinib did better and had responses and remained in response longer without disease progression compared with the patients who were randomized to placebo. That randomized, placebo-controlled trial led to FDA approval of cabozantinib in the second-line setting for patients with iodine refractory DTC [differentiated thyroid cancer]. Bryan, have you had the chance to prescribe cabozantinib to any of your patients?

Bryan McIver, MD: We have a small number of patients who have clearly progressed on lenvatinib, typically, again, after months or years, but once that progression happens, I think we need to be clear about it and not just pretend that everything’s going well. Again, I come back to that transparency and honesty that we’ve spoken about earlier. Once it does progress then, in the past, what we have done is to seek a clinical trial. I would still encourage everyone to seek out clinical trials of newer agents, but now certainly with cabozantinib being approved, we have two or three patients who’ve transitioned on to cabozantinib after progressing on the lenvatinib. It’s great to have another option. The question, of course, will be how long do they last on the cabozantinib? Of course, cabozantinib also has a side effect profile that overlaps with that of the lenvatinib but is a little bit different. The hand-foot syndrome is perhaps a little bit more common; the blood pressure is a little less of a problem. There are some subtleties there, but these drugs still are going to have side effect profiles that are going to need to be managed through the entire journey. However, if we can get three years out of lenvatinib and another two or three years out of cabozantinib, what we all are optimistic about is that in that five-year window we will have the next best thing coming down the highway toward us, and we’ll be ready for the next step on that journey.

Lori Wirth, MD: That is not a pie-in-the-sky idea, right? As you mentioned, 10 years ago we didn’t really have any drugs that had been FDA approved besides just the IV [intravenous] chemotherapy, which we know doesn’t work well. In the past 10 years, we have had seven drugs, I think, that are now FDA approved for iodine refractory differentiated thyroid cancer.

Transcript edited for clarity.

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