Radioiodine Refractory Differentiated Thyroid Carcinoma - Episode 2

SELECT Trial: Toxicity, Duration of Response, and Dose Reduction

Marcia Brose, MD: Of the patients who achieved the partial response in the SELECT trial on lenvatinib, most of these responses were significantly durable. They lasted for many months, and even longer than the 18-month progression-free survival obviously.

In practice, outside the clinical trial, sometimes patients can get a clinical benefit for even longer if the single sites at the time of progression are able to seek out with just radiation or surgery. This is a drug that we now use for an extended period of time in patients.

Unlike other cancers, where the duration of exposure to a drug might be on the order of weeks and months, for patients with thyroid cancer on lenvatinib for anywhere from months to years, it became very important to be able to manage toxicity. The major toxicity associated with lenvatinib and differentiated thyroid cancer was high blood pressure. For that reason, over 60% of patients had to reduce their dose from the starting dose of 24 mg down to either 20 mg or 14 mg within the first 2 months.

These patients actually had to have a dose reduction, but in spite of that did very well. Additional studies are ongoing to see whether we could actually start at a lower dose instead of a higher dose and still get the same efficacy, but the data are not available at this time. Other toxicities that are seen in patients with lenvatinib include loss of weight, particularly loss of muscle mass with sarcopenia, as well as diarrhea. Of course, all these can be interconnected. Fatigue is also another significant adverse effect.

I find that the diarrhea also explains for all these because when patients are not controlling the number of bowel movements they are having a day, they tend to get dehydrated, get more fatigued, and sometimes have more depression, and all these things actually can lead to decrease of efficacy.

It’s really important that patients know how to not only control their blood pressure—which is the thing you have to worry the most in the first month or 2—but also long term, manage the diarrhea, either using Imodium or diet control measures.

In addition, what we do to help patients maintain their weight is to actually have them do strength training. The strength training helps counteract the sarcopenia effect of the lenvatinib and can be very helpful. We prefer not to use dose reduction to help manage adverse effects, but occasionally that can’t be avoided, in which case we often start at 24 mg and then go down to 20 mg. The most common cause for dose reduction in my clinic was patients who have high blood pressure who could not be controlled with 2 or 3 agents.

Occasionally patients also need even more often dose reduction; I tend to use dose interruption. That is a very useful tool to be used a little more commonly, and it’s not uncommon. Especially given what I just said about the GI [gastrointestinal] toxicity, that a 2-week holiday, sometimes for patients who have been on the drug for a couple of years, can really help reset the GI tract, help the diarrhea calm down. Then many times the patients can restart at the same dose and still get the same benefit, but now their GI symptoms are much more controlled.

Rather than using dose reductions, we prefer to use dose holidays. The exception to that is that dose holidays doesn’t help me figure out what blood pressure medicines you need. Because as soon as you restart it, you’re going to need to start the blood pressure medicines again.

But it is important because many of our patients are on multiple blood pressure medicines. If for some reason they go on a dose holiday for GI toxicity, it’s important to remember that they need to stop the antihypertensives that they were on because of the lenvatinib, or they might end up hypotensive.

Transcript edited for clarity.