RR DTC: Managing Adverse Events With Dose Reductions or Holds


Before closing out their discussion on the frontline treatment setting of RR DTC, panelists highlight dose reductions and planned treatment holidays to mitigate adverse events.


Lori J. Wirth, MD: We’ve talked a lot about the toxicity profile of lenvatinib. Maybe we can touch base on what you do in clinic when patients have to have dose reductions, which is baked into the recipe for treating patients on lenvatinib. Ezra, how do you do it?

Ezra Cohen, MD, FRCPSC, FASCO: I give them a dose interruption. There are some differences between different toxicities, but I’ll speak in general terms. Hold the drug, and wait until the toxicity abates or at least gets down to a grade 1. Then it depends on how the patient was feeling and my gestalt about the disease. Sometimes I’ll start at the same dose, although more commonly I’ll dose reduce. From 24 mg, I’ll go to 20 mg; from 20 mg, I’ll go to 18 mg; from 18 mg to 14 mg; and 14 mg to 10 mg. That’s my goal with the usual progression. That’s based on the strength of the tablets. That’s my approach. Keep in mind, if you stop the drug and they are on an antihypertensive, their blood pressure will go down. I tell patients to hold their antihypertensives as well, and to remember to restart the antihypertensive when restarting the drug.

Lori J. Wirth, MD: Thank you for making that point. I was going to make it earlier but didn’t. That’s key. There was a nice abstract presented by Makoto Tahara [at ASCO in 2021], who’s 1 of the SELECT investigators from Japan, looking at how patients did on lenvatinib in a Japanese real-world experience. In particular, how the patients who had received a drug holiday as part of their treatment strategy did. Marcia, did you see that abstract?

Marcia S. Brose, MD, PhD: I saw the abstract. It’s interesting because we already put in a drug holiday. We do that when we need it. Ezra made the point that everything doesn’t happen right away. We tend to not give the dose holiday until they show they need it. At the end of the day, it can be very helpful because they do seem to reset, especially the GI [gastrointestinal] tract, with 1 or 2 weeks off. The diarrhea goes away, and they can rebuild the lining of their GI tract and do quite well. The study looked at planned holidays for lenvatinib, and it showed that patients have significantly better outcomes. In this case, they did the drug holidays that were planned from the beginning, as opposed to later on. [The investigators] showed that patients do quite well with a little higher time to treatment failure, for example. There are data to show that using this approach is very important.

However, [this study] is a little at odds with data from the dose-finding study that says that a higher dose is probably important. We’re talking about cumulative doses, but the higher dose is probably important. I merge the information from those 2 studies when I say that I start at the higher dose. When it looks like they need a break, I start giving the break. But I don’t start with that break up front because dose intensity matters. It was an interesting study, but I don’t think it addresses the entire story, which is that when you can do dose intensity, you should do it; when you can’t, give a holiday. It’s a marathon, not a sprint. Patients are going to be on it for years. They have to live with it, and you don’t want them to be miserable every day. You have to find a way to make it manageable. In the case I presented, this woman was really struggling. But as soon as we started doing that, she comes in and it’s like a normal day. She’s going to work and coming in because this is something she does. It’s almost an afterthought. That 1 week off is what does it for her every time.

Francis P. Worden, MD: I heard you say that patients get used to their new normal. That’s an important thing to tell patients: you’re going to be affected, but this is your new normal. With the breaks, sometimes they’ll say, “Wow.” They didn’t realize how they felt until they went off the treatment.

Lori J. Wirth, MD: To wrap up discussion on this point, optimal symptom management and the incorporation of dose reduction and drug holidays can allow patients to stay on lenvatinib and maintain their beautiful responses for a long period of time. In reality, we have limited treatment options for these patients. Now we have a lot of tricks in our arsenal that we can utilize in clinic to keep patients on therapy for as long as possible.

Transcript edited for clarity.

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