Defining RAI-Refractory DTC and Selecting Patients for Disease Monitoring


Reflecting on a real-world patient scenario of DTC, experts consider how they identify radioiodine-refractory disease and when they would initiate systemic therapy.


Marcia Brose, MD: Can you just wrap up, Lori, by telling us your decision-making process or how you decide to pull the trigger and how it does correlate or doesn't correlate with what evidence is available?

Lori Wirth, MD: This is one of the questions that we struggle with iodine refractory DTC, [differentiated thyroid cancer]: when to initiate the systemic therapy. When I first started doing clinical trials when I was still a fellow, any patient who walked through the door with iodine refractory disease, I'd put them on a trial right away because there were these new oral cancer drugs that sounded great, and then it became obvious that while they are oral drugs and not IV [intravenous] cytotoxic chemotherapy, there still are adverse effects that patients have to contend with. The toxicity can add up over time. The pendulum swung away from initiating therapy early in the disease process to holding off. I've heard a lot of people say that they don't start patients until they are symptomatic or nearly symptomatic, and it's a big question, and we don't have any randomized clinical trials with earlier initiation or later initiation, but it's kind of a unique question in oncology because there aren't too many cancers where we have a good drug like lenvatinib [Lenvima] for example, but we hold off on starting it as long as possible. There are some subset analyses from this select trial with lenvatinib that provide us with some information. One of them that is very pertinent to this case is that there was an analysis done in the patients enrolled in select who had lung masses. There was a subset of patients who didn't have lung metastases, but in the patients who had lung mets [metastasis] at the study entry, there was an analysis of overall survival, progression-free survivals, and so forth in the patients randomized, and lenvatinib versus placebo. And what that subanalysis showed that was surprising is that even when the lung mets were as small as 1 centimeter in size, the patients that were randomized to lenvatinib had an overall survival benefit compared with the patients randomized to placebo even though 89% of patients randomized to placebo crossed over and received lenvatinib at the time of disease progression. And also, the median time to progression on placebo and to cross over was just 4 months. That analysis shows that when the patient has lung mets, if you delay the initiation of therapy, then you might lose out on an overall survival benefit.

Marcia Brose, MD: That probably is the exact same thing that contributed to the over-65 analysis as well, because all those patients crossed over as well, but the only difference between them and the other arm was that they had had a 4-month delay. The other thing that I would bring up—the reason I don't wait for symptoms—is that I have seen on a very regular basis patients that are not symptomatic but they're very close to being symptomatic. If they're right on that cusp and maybe they even start to have a little bit of a cough or something, when I start to treat them, they can sometimes feel worse for a while, and I like to let them, and again, not treat them too early. I don't hold off as much as I did; I've swung 1 way and then a little bit far back the other way and maybe come back to the middle, because if I wait, then sometimes they'll feel so rotten and then they're more likely to say, I need to drop the dose, or whatever, whereas if I get them before they have symptoms, many times while they're responding, they still won't have symptoms, and I think that's maybe the ideal for me. What do you think Bruce, as far as your impressions of this case and how would you have treated this person in your practice?

Bruce Robinson, MD: My initial impression of this man is that he had relatively aggressive disease, as demonstrated by his relatively low thyroglobulin and the fact that his disease was progressing quite quickly. And even though he wasn't symptomatic, I still think that it would be very appropriate to start him on treatment sooner rather than later—certainly, if a person's performance state is just deteriorated, I don’t think they tolerate this group of drugs as well as if they have a good performance status. In terms of this man having radioactive refractory disease, it was clearly demonstrated that he had no uptake on I-131 [radioisotope of iodine-131]-but he did have uptake on PET [positron emission tomography], and that in itself, I think, is sufficient for you to say, yes, this person has RAI [radioactive iodine]-refractory disease.

Transcript edited for clarity.

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