RTP On Demand — Head & Neck/Thyroid | Research To PracticeZETA study of vandetanib in locally advanced or metastatic medullary thyroid cancer
3:27 minutes.
TRANSCRIPTION:
DR COHEN: Vandetanib had been tried in many other cancers, lung cancer included, primarily because of its ability to inhibit EGFR and VEGF receptor. But what people I don’t want to say ignored, but maybe didn’t pay as much attention to, was the fact that it was also a RET inhibitor. So some very clever investigators decided, “Let’s try it in a cohort of medullary thyroid cancer patients,” and, indeed, it demonstrated clear activity, which led to a Phase III study in patients with medullary thyroid cancer. DR LOVE: So let’s talk about the ZETA study that looked at this. DR COHEN: Yes. This was the Phase III study that randomized patients to either vandetanib or placebo. A couple of things to keep in mind with this design: First of all, it only required essentially noncurable medullary thyroid cancer. And this gets back to the issue that we were talking about, where some patients do, indeed, have indolent disease. And we’ll see that in the curves in just a minute. But patients were only required to have unresectable or metastatic disease. Two-to-one randomization, PFS, progression-free survival, was the primary endpoint. And here we see that this was a positive trial, clear benefit in progression-free survival versus placebo. But if we look at the placebo curve for just a minute what we can see is that the median PFS on placebo was almost 20 months. And at a year, more than 50% of patients did not have progression on the placebo arm. So clearly, there is a cohort of medullary thyroid cancer patients who have disease that’s not growing rapidly. Nonetheless, no doubt that this was a positive trial. DR LOVE: Have people ever talked about using calcitonin doubling times to try to pick these people out? DR COHEN: Sure. That’s used more in when to decide to initiate therapy, but that’s a typical parameter that we follow, calcitonin. We know that patients whose calcitonin doubling time is less than a year will have a more aggressive course. DR LOVE: So any other comments? I see that a number of the placebo patients responded when they crossed over. DR COHEN: Exactly. And that’s why progression-free survival was the primary endpoint, because when patients crossed over, they appeared to have the same benefit especially with respect to response rate, as the patients who were initially randomized to vandetanib. So clearly active drug, 45% response rate, biochemical responses in vandetanib-treated patients and a difference in time to worsening of pain. So some symptomatic improvement as well. DR LOVE: And I want to ask you about that, but also in terms of the REMS program that comes along with it. How does that work? DR COHEN: It’s a very easy-to-navigate program, but it’s a program that was essentially mandated by the FDA because of the QT prolongation. So for instance, a prescriber needs to take a short online course to be able to prescribe the drug. Then every patient who gets the drug gets enrolled in this program. It’s quite helpful. The patient gets educational materials. The physician gets reminders with respect to especially how to manage the QT prolongation. And so it’s really a program that’s designed to prevent fatal complications from the QT prolongation. |