Soft Tissue Sarcoma Update, Issue 1, 2017 (Video Program)Activity and tolerability of the tyrosine kinase inhibitors regorafenib and pazopanib in patients with STS
3:45 minutes.
TRANSCRIPTION:
DR VAN TINE: When you start talking about tyrosine kinase inhibitors, including — we have an FDA approval for pazopanib. Two years ago, a group I was involved in recently published a paper on tivozanib as active, and now regorafenib. A lot of these are just dirty tyrosine kinase inhibitors. The regorafenib trial took all soft tissue sarcomas that were high grade, then allowed them on trial and found that regorafenib seems to have a signal of activity. I think that this is something that I wouldn’t jump to using yet. I think it’s something where a lot of clinical trials need to be finished or further exploited so that we know where that drug may fit in in soft tissue sarcoma. Because you get into that data, you begin wondering what sort of signal you’re actually looking at in the subset analysis. And so what we’re hitting — I think a lot of the targets in sarcoma, in terms of their tyrosine kinases, are really unknown. And my hypothesis is really that the reason we’re finding a lot of these dirty drugs have activity is you’re hitting different things in different sarcomas and at least seeing activity. DR LOVE: So I see actually this trial, REGOSARC, was published in Lancet, I think? Yes, Lancet Oncology. I don’t know if it’s the same data set that was presented at ASCO. But they’re conclusion is that it has “an important clinical antitumor effect” — this is single agent, right? DR VAN TINE: Yes. DR LOVE: “In nonadipocytic soft tissue sarcomas, improving progression-free survival.” Do you think that’s true? DR VAN TINE: I think that that is probably true. I think that where we’re going to put that drug is, it needs a lot more work, to be honest. And I wouldn’t want general practitioners just randomly writing it. DR LOVE: Interesting. I wonder, what did they say in terms of tolerability? That’s such an issue with colon cancer. Did they use the same dosing? DR VAN TINE: Yes. No. What’s interesting, we go to these ad boards, and so if you go to an ad board for pazopanib and they meet with all the renal doctors, and then they come to the sarcoma doctors. And they sit and they’ve heard that this is just a horrific drug. And then come to the sarcoma doctors, and we think it’s great. I think, in our experience, because the GIST patients have come off sunitinib, they like regorafenib, and our patients have come off chemo, that these seem to be better tolerated in our patient population because I think it’s perspective. DR LOVE: Hmm. That’s interesting. As long as you brought it up, what about pazopanib? We got a couple of questions about that. What’s the role, in your own practice, outside a trial setting nowadays in terms of pazopanib? DR VAN TINE: I think pazopanib is a really useful drug. I think it’s got some dosing complications in the soft tissue sarcoma realm that I think are soon to be addressed with new trials. But I think it causes diarrhea. I think it causes fatigue. And I think that there’s a hepatotoxicity that has a black box warning. But beyond that, if you can get the dosing right, I personally use a dose escalation that’s not on label to get the tolerability in my patients to where it needs to be. I think it’s a good drug. And there is a subset of patients where that is a really good drug. I’ve had some patients with, I know it’s not a soft tissue sarcoma, but, say, myxoid chondrosarcoma. They seem to go on that for years. I’ve had some synovial patients. They do go on it for just unbelievable amounts of time. And I know these are all extreme responders, but it is a really good drug for the right patient. |