Factors in Selecting Treatment for DTC

Reflecting on the first patient scenario of radioiodine-refractory DTC, experts share their considerations for optimally selecting and sequencing therapy in this setting.

Marcia Brose, MD
: Let's get to the discussion. I'm going to turn this over to my colleagues. Let's start with Dr Wirth. Can you describe your initial impressions of this case and how you treated patients like this in your practice?

Lori Wirth, MD: I'm glad that you chose this case. It's a very interesting case, perhaps unusual with the multiple nodal recurrences in the neck, and the number of prior surgeries that he had. I would imagine that the morbidity of the numerous surgeries added up over time, then you put external beam radiation on top of that. I'd be concerned about his neck and fibrosis and the sequela of that.

Marcia Brose, MD: That's a good point, I will point out that his neck has looked better than many, many other patients who have had that in their neck. And he had already had, as you pointed out, 5 surgeries and external beam radiation before I ever even met the man. But remarkably, he has not had trouble with things like strictures in his throat or difficulty swallowing and things like that.

Lori Wirth, MD: When you were on about the fourth surgery, I was thinking, when is she going to mention radiation therapy? And 1 of the reasons why I thought that aspect of the case is so interesting is because we've really steered away from using radiation therapy for these patients and using it as a tool very selectively because of the long-term sequelae. As well as you're not curing anybody to subject them with that; that kind of toxicity is a big deal for a palliative therapy. But at some point after—I'm not sure what the right number of years is—but at some point, radiation is definitely going to make sense. We probably would have made that decision. And can I say 1 other thing about the case I thought was great—and you already addressed this and talked about it—but the fact that the patient had a BRAF V600E mutation, that's the most common mutation that we see in papillary thyroid cancer. And in this era of precision medicine, it's tempting to think that you'd pick a BRAF-specific therapy for the systemic therapy for a patient like this. It's a very good teaching point that the data that we have is with either vemurafenib or dabrafenib or dabrafenib plus trametinib. The data just don't look like we see as much efficacy with the BRAF-directed therapy as with lenvatinib, which is interesting because that's often not the case.

Marcia Brose, MD: I’m interested to see what some of the newer BRAF inhibitors might improve. But at this point, I agree. And for that reason, it is sort of down my list a little bit. What do you think, Dr Robertson?

Bruce Robinson, MD: I agree with what Lori has said. We would probably have moved in earlier with external beam radiotherapy. These days, external beam radiotherapy is much more focused than it used to be. And the toxicity and morbidity associated with it is a lot less than perhaps many of us have grown up with. I also agree that we would generally try to start such people on TKIs [tyrosine kinase inhibitors] such as lenvatinib in the first instance before we would consider a targeted therapy with dabrafenib and trametinib, and the toxicity associated with both of those agents is not trivial. The 1 thing that I suppose does surprise me is that you were able to keep this man on 24 mg of lenvatinib for about 8 months. That's quite extraordinary. I've had a couple of people who've tolerated such doses, and I always start them on 24 mg because that's what the data says, but not many of them are able to tolerate this sort of dose. As we get a better understanding of lenvatinib, perhaps even become able to measure it in the blood, we may be able to adjust and modify doses better to suit individual patients than we currently do.

Marcia Brose, MD: That initial hit with the 24 mg though, is important. And that's probably why we have the noninferiority that we saw in the dose-finding study. Because even if they're only on it for 2 to 6 months at the higher dose, it does make a difference, and that's the importance of starting at that dose. It's interesting.

Bruce Robinson, MD: My practice is to try to maintain people on 24 mg if they can possibly tolerate it for 2 months, and I give them that expectation at the beginning. It's important to set patient's expectations too. And I've been selling 24 mg for 8 weeks on the basis of, if you get hypertension, that's going to be a good thing, because we know from the work that Lori did and published, that many of us were involved in, that that higher dose associated with hypertension was also associated with better outcomes.

Marcia Brose, MD: Do you want to tell us a little bit about what stage?

Lori Wirth, MD: May I please ask a basic question of our endocrinologist here? Marcia mentioned that that the patient had radioiodine treatment but had not been on a proper low iodine diet leading up to that. Bruce, later the patient had the low-dose whole-body scan that showed no uptake, so I think I agree that confirms iodine refractory disease. Then the PET [positron emission tomography] positivity kind of seals the deal. But Bruce, would you have been tempted earlier on in the case to circle back and give him another proper dose of radioiodine?

Bruce Robinson, MD: Look, I probably would have before I would just define a patient or describe a patient as being radioactive iodine-refractory. I like to do that with a decent therapy dose rather than a scan dose. But as you know, in the process of rewriting the ATA [American Thyroid Association] guidelines, 1 of the things that's come up is the role of low iodine diet, particularly, and the evidence is not all that strong that it makes a massive difference. If the patient had been given iodine contrasts as part of the scan, then that might be a different story, but I don't think there's a lot of evidence that the low iodine diet makes a huge difference, unless, of course, a patient is taking iodine supplements or eats a lot of Japanese foods. We kid ourselves a little bit about the importance of this, and it does create yet another stress for patients.

Transcript edited for clarity.

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