DR LOVE: Right now, are you using sorafenib outside a trial setting in your patients? And in what situations, Jorge?

DR CORTES: Yes. I mean, not only us. I am. I definitely am using sorafenib. And when I don’t have a clinical trial, that’s the one I try to incorporate into some combination with chemotherapy. And I see it used a lot. And I have a lot of patients that are referred to me that have already gone through sorafenib being used in the community setting. Some third-party payers are covering that. Others are not. So you have to check. But it is being used very, very widely for these patients. It’s become like the standard.

DR LOVE: So again, Rich, are you using sorafenib?

DR STONE: No. I don’t have any problem with it being used. We still have a clinical trial that we’re putting all our FLT3 patients on, so that gives me a little bit easier answer to that. But if I didn’t have the clinical trial, I wouldn’t use it yet.

The so-called SORAML study, published in Lancet Oncology by Chris Rollig showed a relapse-free survival benefit and event-free survival benefit but no overall survival benefit. So I don’t think it’s wrong to use it. I don’t routinely use it. It might add toxicity without known benefit. I’m a bit more conservative, medically, at least, that way, but I think it’s an open question.

DR LOVE: I’m going to ask Jorge to respond, but first, really quickly, I wanted to find out if the 3 of you use sorafenib right now. Do you use sorafenib?

DR COLE: I’ve only used it once in a patient who had an FLT3 mutation and had blown through everything else.

DR JOHL: We have used it on 3 or 4 patients, sorafenib, and actually our turnaround time for FLT3 is within a week. So by the time the patient’s done with induction, 7 + 3, we add sorafenib on day 8. And we do that for 10 days.

DR FEINSTEIN: Yes, I have used sorafenib in patients generally who are older, who I am still contemplating getting to transplant.

You said it doesn’t alter overall survival. Do you think that it improves the complete remission rate, the addition of sorafenib, which then may make a patient a better candidate for a nonmyeloablative allogeneic transplant, let’s say?

DR STONE: In the SORAML trial, it didn’t really improve the complete remission rate, but it probably led to deeper remissions. Probably, although curiously in that trial an uncensored analysis didn’t show a benefit for the sorafenib, which was weird. But I think it’s reasonable. It probably does produce deeper remissions. We don’t really know that. And if it produces deeper remissions, they’ll do better with transplant.

DR LOVE: Just out of curiosity, Jorge, what have you seen in terms of tolerability issues, if any, with sorafenib in the AML setting? Obviously it’s used in other cancers.

DR CORTES: Yes. That’s an important question. And that brings me back, also, to some of the things that were mentioned earlier. I think sorafenib — and I use it. And I think we can. It’s manageable for most patients. But it does have toxicity. I mean, it does have more issues with safety. And when you combine it with chemotherapy it adds to that, and you see some liver toxicity. You see some effusions and things like that. I’ve seen hand-foot syndrome. So there’s no question that it’s a little bit more of a complicated drug to use. Again, usable and I use it a lot, but I think it is more difficult to use.

I’ll go back, also, to some of the comments that Rich made about this other study, the sorafenib, the SORAML study. And it is true. It didn’t prolong survival. And the other thing that’s important is that also, the Germans did a study in older patients, also a randomized study of chemotherapy with or without sorafenib. And that study was not positive.

Now, it was all comers, not only FLT3-mutated patients. And the percentage of patients with FLT3 mutations was a little bit lower, because these patients tend to have more secondary leukemias that don’t have as many FLT3, et cetera. But I mentioned that I would like to use this in older patients, and I still maintain that. But at least with sorafenib, we have that 1 randomized study in older patients that was not a positive study.

And the last comment I’d like to make is about this issue about the waiting and just to remind people that these patients do tend to be a little bit more proliferative. So these are the kinds of patients that sometimes you cannot wait that much. So, therefore, this adding it on day 8 becomes even more relevant. The key here would be that diagnose the patient. You measure the FLT3. If you have to start treatment, you start treatment. But at least you’ve got the test cooking, so that you can start as soon as you get it back.

Module 1: Current and future approaches to targeted therapy for acute myeloid leukemia (AML)

Module 2: Other clinical issues in AML management

Module 3: Case discussions