RTP On Demand — Head & Neck/Thyroid | Research To PracticePhase III SELECT study of lenvatinib versus placebo for radioiodine-refractory differentiated thyroid cancer
5:19 minutes.
TRANSCRIPTION:
DR COHEN: So a very interesting study. Again, taking a group of patients who had differentiated thyroid cancer, were refractory to conventional therapy — that is, radioactive iodine — and randomized patients to either lenvatinib or placebo. There was 1 key eligibility criterion and part of the screening process that differentiated the study that’s worth pointing out. And that is that patients had to have progressive disease — and that was true of the sorafenib trial, as well — but that progression of disease had to be confirmed by an independent party. And so now we had patients enrolling on this trial that not only had to have progression within a year, but that progression had to be agreed upon by 2 separate individuals. And so what we ended up seeing was essentially a group of patients as judging by the placebo arm, who had more aggressive disease. And what we saw in terms of the results, primary endpoint being progression-free survival, was that lenvatinib produced about a 60% response rate, 6-0, with some complete responses, although the rate of complete response was low, but a progression-free survival difference that was, I would say, quite extraordinary: a hazard ratio of 0.2, a median progression-free survival in the lenvatinib arm, about 18 months, median progression-free survival in the placebo arm about 3 months, clearly a dramatic difference. What we saw at this year’s ASCO were mature data on overall survival. And although the curves do begin to separate for overall survival, it didn’t reach statistical significance. And we do have to say that there is no difference in overall survival between the 2 arms. And I think the reason behind that is that, as you can imagine, many patients — in fact, the great majority of patients — did end up crossing over either to lenvatinib itself or to some other TKI, and, therefore, are really diluting any effect on overall survival that we were going to demonstrate. DR LOVE: There were a couple of papers at ASCO related to that that I thought were interesting. One, Marcia Brose presented an interesting poster on age and lenvatinib treatment in terms of survival. And then there was another poster looking at lenvatinib with or without prior VEGF therapy. Any comments on those two? DR COHEN: Yes. I think both those data sets are really important when we begin to think about which patients we should be treating and how to treat patients with differentiated thyroid cancer with this drug. So the Marcia Brose poster really looked at age and the utility of the drug and found that the drug was quite effective, in a sense irrespective of age. The conclusion was that it was effective in patients greater than — I believe the cutoff was 60, maybe 65. It was effective in that group of patients, which is something that we wondered about. Are these drugs as effective in an older patient population versus the younger counterparts? And it was clear from that analysis that the answer is yes, and, in fact, just as effective. DR LOVE: If I understood that correctly, though, the people who didn’t get lenvatinib, the older patients did worse than the younger patients. And then, by getting treatments, it equalized. Is that the way you read it? DR COHEN: Yes. That’s exactly right. Lenvatinib appeared to, in a sense, do exactly what we want, and that is change the natural history of the disease, whereas we had a group of older patients with thyroid cancer who, unfortunately, tend to do worse. DR LOVE: Is that biologically, the tumors are more aggressive? DR COHEN: They are. It’s a disease where age actually factors into the staging and is an important prognostic feature. And so it’s taking a group of patients who prognostically usually do worse and really flipping that. In fact, having them do just as well as the younger counterparts suggests that you’re really changing the natural history of the disease. DR LOVE: So the other paper looked at prior TKI therapy. You were talking before about that that it seems like the response seems to go down. But here it seemed like it was about the same. DR COHEN: Yes. And there was a hint of that in the original presentation, but it wasn’t really fleshed out very much. And here, in the abstract that was presented at ASCO, it focused on that. And that’s exactly true, that for patients who had had prior TKI therapy — and, for the most part, that was sorafenib — the efficacy seemed to be completely maintained. |