My Treatment Approach: Applying Evidence to Clinical Practice to Improve Outcomes in Differentiated Thyroid Cancer - Episode 5

Optimizing the Use of Lenvatinib in DTC: Patient Selection and Dosing

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Shared insight on selecting appropriate patients for lenvatinib therapy in differentiated thyroid cancer, as well as optimizing dosing strategies in the context of clinical trial data.


Marcia Brose, MD: Let me ask Bruce another question. What role does age play when you decide whether to use lenvatinib? Tell us what data might affect your decision.

Bruce Robinson, MD: It’s not so much age that affects my decision, it’s the patient’s performance status. That’s the most important thing of all because as you know some group analysis in the SELECT trial showed that age was not a factor and that patients who were older responded just as well, in fact slightly better than, patients, ironically who were younger. Chronological age is not what counts, it’s performance status that counts.

Marcia Brose, MD: That’s a good point, and especially comorbidities. But interestingly, when the subanalysis was done in SELECT, even with comorbidities being worse in the older patients, they still had an overall survival advantage. That probably is because those patients are more likely to have trouble if their disease progresses. Of course, treating them slows that, and if that’s the thing that’s going to shorten their life span because they’re closer to death, then obviously treating with lenvatinib is better than not. But it was an interesting, unexpected result from SELECT. Lori, do you have any kind of criteria that you usually use when you decide when to start lenvatinib for patients with DTC [differentiated thyroid cancer]?

Lori Wirth, MD: Sure, you two already discussed the starting dose, and I agree completely. The information we have are 2 randomized trials that tell us there’s a proper starting dose, and that’s 24 mg. The randomized study that you discussed, the noninferiority study comparing the lower 18-mg dose and the 24-mg FDA-approved starting dose, provides as much data as we need that tell us that 24 mg is the right starting dose. There are times when we’re treating elderly or very frail patients with multiple comorbidities that I don’t start at 24 mg, but we know that 24 mg should be the default starting dose for most patients.

The other thing is, we all are very familiar with dose holds and dose reductions, as well as managing the toxicities with supportive care. When you do have to dose reduce from 24 to 20 mg, it’s not a failure on anybody’s part. That’s part of taking care of patients on lenvatinib. It’s expected at some point that most patients will have to have a dose reduction, and it’s perfectly fine. It was Bruce who did that analysis that took a look at the response on the SELECT trial over time, and you see the biggest drop-off in the tumor measurements in the first 2 months on SELECT. And the median time to the first dose reduction was right after the 2 months. It’s on that 24 mg that almost everybody’s on where you see the most significant decrease in the tumor measurements. It seems like that’s important somehow.

Bruce Robinson, MD: The other thing to add there is that we talked about this not being a failure. Patients often see it as a failure, and it’s really important again in setting patient expectations to make them realize that it’s not about being on the biggest dose for the longest time that will save their lives. It’s about being on right dose for the longest time because they can die and suffer from morbidity and toxicity just as much as they can die of disease. Having them understand that is a balance between those 2 things is important.

Marcia Brose, MD: What blew me away about that study, the dose-finding study as well, is the third end point was quality of life. I was sure that the quality of life was going to be better if they started at a lower dose. And what Matt Taylor, [MD], presented in the manuscript that is in press right now, is the fact that even starting them at a lower dose, their detriment in quality of life was minimal, and it was exactly the same as 24 mg. In other words, the impact of starting therapy was the impact of starting therapy, and it wasn’t dependent on dose. I was totally stunned with those data, and if anything, that also sealed the deal with saying we should start on 24 mg. Lori, you were smiling. Were you also surprised?

Lori Wirth, MD: I think everyone was surprised. And there have been a lot of providers who were using a lower starting dose because they were convinced that it worked as well and that patients did better. The reason I was smiling was because I’ve just been looking into the idea of equipoise, particularly in the setting of clinical trials. Equipoise from an ethical point of view is so important in a randomized trial. And this is exactly one of the reasons why it’s not too hard to have equipoise, because we can think as experts that we know how to best do things. But you need clinical trials to show that. With equipoise, if you have a different expert saying, no, 24 mg is the right starting point, then the equipoise is between the 2 experts who really know the field well and they have a difference of opinion, so we need the clinical trial to show us what the right way is.

Marcia Brose, MD: It also emphasizes the benefit of it being a blinded study because I’m sure that I would have been telegraphing to my patients, “Oh this is going to be much worse. You’ve got the 24 mg, sorry for you.” And instead, of course, we all were giving 4 tablets, and we didn’t know what we were giving. So both the provider couldn’t telegraph what they were expecting, nor could the patient. I thought it was really an interesting study. I realize we should probably be doing things blinded as often as possible for that equipoise reason exactly.

Transcript edited for clarity.