RTP On Demand — Head & Neck/Thyroid | Research To PracticeTreatment algorithm for radioiodine-refractory differentiated thyroid cancer
4:46 minutes.
TRANSCRIPTION:
DR COHEN: When we approach patients with radioiodine-refractory differentiated thyroid cancer, we now have a couple of options that are FDA approved. One is sorafenib. One is lenvatinib. And, when I look at the data, we have to keep in mind that these were 2 separate Phase III studies. There were similarities between the trials, but there were 2 separate trials, so not completely fair to compare them. But when I look at the data, what comes out at me is that lenvatinib has a high response rate. It’s about 60%. And the group of patients that were enrolled on the lenvatinib trial, if you look at the placebo arm, appeared to have more aggressive disease: placebo arm, median PFS of just over 3 months. And yet lenvatinib produced a hazard ratio of around 0.2. The median PFS in the lenvatinib arm was around 18 months, suggesting that lenvatinib is a potent drug in patients with radioiodine-refractory differentiated thyroid cancer. And the paradigm that I use in treating patients, and that I think that many people use in oncology, is you go with your best drug first. And even though there isn’t head-to-head comparison, my sense of the data is lenvatinib is quite effective. And so for most patients, not all, I use lenvatinib first. These are some patients — for instance, the most common scenario is difficult-to-control hypertension, where I know lenvatinib has hypertension as a primary side effect, where I may go to sorafenib. Other patients may include those who have abdominal issues, where lenvatinib, in my experience, has had more GI side effects. And so sometimes the baseline functioning of the patient may influence, or their comorbidities may influence which drug I use first. But I would say, in general, it’s going to be lenvatinib. DR COHEN: In some patients I go to sorafenib. To be honest, in many patients I may choose a drug that’s not approved, such as pazopanib or even sometimes axitinib. Of course, the fact that they’re not approved can make it logistically difficult to obtain. But in general, lenvatinib is my first choice. Second choice is another TKI. I know I’m not going to get as much bang for my buck in that TKI. That is, I’m not going to get as much progression-free survival or a higher response rate. But other TKIs do seem to work in that second-line setting, if you will. DR LOVE: So, ideally, if you didn’t have these reimbursement issues, and indirectly comparing, I guess, a second-line therapy, how do you compare those 3 TKIs? DR COHEN: Yes. Again, difficult to say because there are no head-to-head comparisons, unfortunately. And there probably never will be. But again, when looking at the data, when looking at the toxicity profiles, I like axitinib. It’s an effective drug and it’s really quite well tolerated. And so if I had complete freedom to chose whatever TKI in that second line, if you will, I would probably choose axitinib first. Pazopanib after that. Pazopanib is a very effective agent, high response rate. Relatively well tolerated, but I think not as well tolerated as axitinib, at least in my experience. DR LOVE: And then do you see patients getting to third- and fourth-line therapy? And what do you do there? DR COHEN: We do. So for third-line therapy, I will actually try to use another TKI. And what happens with sequencing these TKIs is that you get lower response rates and shorter durations of response at every line of therapy, as you might guess, but it’s not zero. You do still get some benefit. And so even in the third line, I’ll try another TKI. And again, if I had complete freedom, that would be pazopanib. Now in the fourth line, it really does become challenging. Because by the time we get to the fourth line, the TKIs are minimally effective. And then we really are at a loss. We don’t have a good therapy in that instance. Sometimes I would introduce an mTOR inhibitor such as everolimus or even sometimes temsirolimus. Or really try to look for a clinical trial. |