RTP On Demand — Head & Neck/Thyroid | Research To PracticeBRAF inhibitor treatment in differentiated thyroid cancer
3:06 minutes.
TRANSCRIPTION:
DR LOVE: So let’s talk about what we do know about BRAF inhibitors. And maybe you can comment on this paper. DR COHEN: This was one of the initial reports of BRAF inhibitors working in patients with papillary thyroid cancer. And this was not restricted to thyroid cancer. These were 3 patients who were treated on this clinical trial. And what the investigators from MD Anderson saw was 1 patient was a partial response, and then 2 patients with stable disease. And this, of course, prompted further study. And that study was a Phase II study with 2 cohorts, one a VEGF receptor-naïve cohort and the second a VEGF receptor inhibitor pretreated patients. Both enrolled about 25 on each cohort at the standard dose of vemurafenib, looking for responses in progression-free survival. Here you see that we, in fact, did see activity in both cohorts. About a third of patients in the naïve and in the pretreated cohorts responded to vemurafenib. We saw most patients with some degree of tumor shrinkage. DR LOVE: So typical driver mutation type of story, but also in terms of progression. How long do these responses last, and what happens on progression? DR COHEN: Yes. Keep in mind that this was a smaller study. We’re talking about 25 patients in each cohort. One thing that was different, perhaps, than the melanoma, whereas in melanoma we see responses with BRAF inhibitors, but those responses tend to be short lived. Here we saw more durable responses, especially in the naïve population where we saw some patients who had durations of response over a year. So maybe there are some differences in what happens when patients are treated between melanoma and thyroid cancer. DR LOVE: Any comments on this paper? I was surprised at this. It was looking at dabrafenib, but in an attempt to, I guess, reactivate or redifferentiate response to radioactive iodine. DR COHEN: Yes. This comes from preclinical work, mostly out of Memorial Sloan-Kettering, that showed that inhibiting the MAP kinase pathway either with a MEK inhibitor or a BRAF inhibitor could actually resensitize thyroid cancer cells to radioactive iodine. And it has to do with how the sodium iodide symporter is expressed in these cells. And so in preclinical models, that appeared to be true. And then the group from Mass General used a BRAF inhibitor in a pilot study, 10 patients, asking the question, Can dabrafenib, short-course dabrafenib, actually reinduce radioactive iodine uptake? That was the primary endpoint. And with the new radioactive iodine uptake, can we actually see responses? And the answer to both questions was yes. So 6 of those 10 patients had reuptake of radioactive iodine, and 4 of those 6 actually had responses. |