Case 2: Systemic Treatment Options


Experts in the management of thyroid cancer share their treatment recommendations for a 60-year-old man with RET+ metastatic medullary thyroid cancer.

Lori Wirth, MD: Andrew, Marcia, which systemic therapy are you going to recommend for this patient? Assuming you cannot offer a clinical trial to the patient, you have 4 choices.

Marcia Brose, MD: I’ll take a stab at it. I think that I’ve already tipped my hand, I like the second-generation targeted therapies, the RET-targeted therapies. Interestingly, both vandetanib and cabozantinib are also RET inhibitors, as well as multikinase VEGF receptor inhibitors. However, the selective RET inhibitors seem to do better as far as overall responses with less toxicity. I’m a big fan of these agents, both agents are ones that I would consider, and sometimes the decision comes down to which one I can get more easily for the patient through their insurer, through their specialty pharmacy. I think they’re both excellent choices, and overall [adverse] effect profiles are at most 25% of the severity that we’re seeing with a multikinase inhibitor. With that, I’ll let Andrew tell me what his favorite is, I can guess.

Andrew Gianoukakis, MD: Yes, I completely agree. That’s one of those no-brainers; the drugs are as efficacious and have a fraction of the toxicity. In a patient with a RET-mutated MTC [medullary thyroid cancer], I think you would go with pralsetinib or selpercatinib. The question is, which one is on their insurance plan? There are some small differences, like once a day versus twice a day, and there are some small differences in the subtypes of mutations. However, the drugs are pretty identical, and it’s a toss-up which one you would reach for.

Lori Wirth, MD: Can I just ask quickly; this patient…he has very aggressive, rapidly progressive disease. When to start therapy is a no-brainer. However, there are patients who do have less virulent disease, where they might be asymptomatic, but they’re rather slowly progressive over time. Is there a right formula for when to start therapy?

Marcia Brose, MD: I think my formula for starting therapy is when I think that progression is going to start risking development of symptoms. We kind of mentioned this before, but the problem when you start therapies when there are symptoms going on, is now you’re adding any toxicity from a drug on top of symptoms. I still want to avert the development of symptoms. There are some patients with very indolent disease, so I think there’s a role of active surveillance in medullary thyroid cancer as much as there is in differentiated thyroid cancer. I usually get 2 time points; I think this patient certainly declared themselves early, so there’s not as much room for active surveillance here. However yes, absolutely, you want to make sure. Although these are well tolerated, it might still be a while before they need it; the longer they can go without any cost burden or adverse event burden, you’re just protecting that time for them. Once they start, they’ll usually stay on the drugs for the rest of their life.

This transcript has been edited for clarity.

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