What is Radioiodine-Refractory DTC?

Marcia Brose, MD: One of the most important things in giving patients lenvatinib or any of the agents for systemic therapy of differentiated thyroid cancer is being able to define the population that would most benefit. These agents are approved only if they’re radioactive iodine-refractory patients. That means that iodine has been used in the past and either was not absorbed by the cancer, so they’re iodine nonhabit, or was taken up by their cancer but they proceeded to progress anyway. In which case that patient would be considered radioactive iodine refractory.

In the actual trial there was another criterion that if patient had exceeded 600 millicuries, they’re also basically considered radioactive iodine refractory. That tends to be a little more of a controversial criterion but certainly was important in the study. In most patients, the basis is that most patients, if they’re going to get a benefit and be cured by radioactive iodine, usually are cured by the time they’ve had 400 millicuries and certainly by 600 millicuries. That’s the justification for that, although it was rarely used in the study.

Patients who now are being treated occasionally with lenvatinib. Some of them are not even eligible for radioactive iodine, and this includes patients who have large masses in the neck that are not amenable to surgery. When patients have a full impact thyroid gland, radioactive iodine is not indicated.

There are some approaches to make them radioactive iodine amenable by trying to ablate the thyroid using radioactive iodine first and then doing a treatment dose. However, in our experience, if we do that, we still end up with a tumor that obviously was more aggressive, possibly more poorly differentiated. In most cases those patients won’t pick up iodine anyway. In general we tend to say that patients who still have an intact thyroid due to a basic cancer are in general a patient profile that I would not find amenable to radioactive iodine therapy.

For patients who do have radioactive iodine–refractory differentiated thyroid cancer, sorafenib and lenvatinib are now approved by the FDA, the European Union, and many countries globally for the treatment of this cancer. Sorafenib was approved initially, and lenvatinib was approved 2 years later.

How I decide which to use is an interesting question, because there can be some times when I’ll prefer 1 over the other. In most cases I tend to pick lenvatinib first. The answer to why that is: We already know we have good data that show, from the Journal of Clinical Oncology paper, that patients who are over 65 years old, if they get lenvatinib, are more likely to have an increase in overall survival. That has not been shown for sorafenib, and for that reason for patients over age 65, as a general rule I will choose lenvatinib first.

A reason not to take lenvatinib goes back to the AE [adverse-event] profile. For a patient who has a lot of trouble controlling their blood pressure, and I do have 1, who’s already on 3 blood pressure medicines without being on lenvatinib, it’s going to be very difficult to control if they’re started on lenvatinib. Those are the patients that I might start first on ceritinib.

I have to pick and choose a little which patients I use. But in most cases lenvatinib—given its really good response rate of over 60% and its fairly well-tolerated adverse-effect profile—in general is my first choice of treatment.

There are some patients who might have more indolent disease. With some countries, because of approvals, sometimes lenvatinib is not available, in which case obviously sorafenib would be used first. But in cases where both are available, it is important to know that if you did have to choose sorafenib first, or if the patients have been on sorafenib for a while, maybe before lenvatinib was approved in your country, there were interesting data from the SELECT trial that said that if they received lenvatinib in the first line, they got 18-month progression-free survival. But if they received it in the second line, and in most cases it was second-line sorafenib, the progression-free survival was 15 months, which is still rather good.

Virtually all my patients will be exposed to lenvatinib unless there’s a very strong contraindication. For the most part, I find this helps most of my patients have a very good progression-free survival.

One caveat is that because of the toxicity profiles, they are not insignificant, they can be dangerous. It’s important that the person—not the investigator but the practitioner who’s prescribing it—has a close relationship with a patient. Because of the blood pressure issues, we recommend patients come in every 2 weeks for the first 2 cycles to make sure their blood pressure is well controlled. Sometimes what we’ll do is actually give them the prescription for an antihypertensive, so if it starts to go up while they’re at home, between visits, they’re able to go to a pharmacy and actually get a prescription filled in time to be able to bring that blood pressure back down.

Managing adverse effects is not trivial with lenvatinib or sorafenib. It’s very important to have a close relationship with a patient, especially good communication during those first 2 to 6 months to manage any adverse effects that might be coming up.

Transcript edited for clarity.