Update on Advanced Breast Cancer Treatment - Episode 7
Transcript:Adam M. Brufsky, MD: Right. So the last thing we’ll talk about in terms of these targeted therapies is we have one that’s already been approved. Where does it fit in now, I guess it’s the old school one, this is old school which is everolimus. Where do we put everolimus, Hope, guys, any questions?
Hope S. Rugo, MD: It’s an interesting thing. Joyce and I were talking about mouth sores about three or four years ago around when, close to when it was approved, and the oral medicine people were very interested in using these steroid dental pastes that they use for aphthous ulcers and started using a steroid mouthwash, I think, that was originally developed by Joyce’s nurse or at least put forward.
Adam M. Brufsky, MD: She patented it.
Hope S. Rugo, MD: Yeah, it was pretty interesting and we stopped seeing the mouth sores. So, actually, we’ve all done now trials looking at steroid solutions. We used a commercial steroid preparation with dexamethasone, and Joyce, you’ve been doing one with those compounded formulation. And we’ll have some data we hope to present at ASCO on our single arm trial showing that you can essentially close to eliminate any significant mouth sores. So that makes everolimus a lot easier to use because I think that those early mouth sores, most of them occur in the first six to eight weeks, is a real big issue. Interestingly, we just actually are publishing a paper from some data we did looking at a meta-analysis of a lot of trials with everolimus in different solid tumors, showing that the people who had stomatitis and who got delayed and had dose reductions, did just as well if not better than the people who didn’t have stomatitis.
So it may be, when you’re not steroid prevention, a marker of drug exposure to some degree. I’ve seen patients respond really well to everolimus, even those who failed palbociclib. People who were on PALOMA-2 progressed, were unblinded, were on palbociclib, went on everolimus and exemestane even after three lines of chemo and it gave them their only six months off of chemotherapy. So I think that everolimus has a continued place. What will happen if we develop a PI3 kinase inhibitor that can be approved and is tolerable—that’s another question. That could replace everolimus, but right now, I think it still stands on its own. I don’t know what everybody else thinks.
Christy A. Russell, MD: I agree. I’ve been using the dexamethasone elixir, the commercially available one. I don’t see stomatitis at all anymore. I still see intermittent non-infectious pneumonitis and that’s what I’m targeting right now. That’s the toxicity that I’m targeting right now.
Adam M. Brufsky, MD: Yeah, that to me, that’s a scary one.
Christy A. Russell, MD: I just want to make sure you don’t miss that one.
Adam M. Brufsky, MD: That’s a really good point to say to the audience that you have someone who comes in coughing, short of breath, you do a CT scan. She has what may look like lymphangitic spread and then the light bulb hopefully will go off in your mind that, oh, she’s been on everolimus for six months. This is a pneumonitis. Before you immediately go to chemo, withdraw the everolimus for a while and see if she gets better.
Hope S. Rugo, MD: Even steroids. The thing is I think if you educate patients well and you’re doing regular scans, you often just pick up grade 1 and it never goes anywhere. But if you tell people to call in if you have little symptoms, you don’t ever get to that really bad shortness of breath.
Joyce A. O’Shaughnessy, MD: Exactly. And I don’t know if you’ve seen it. I think this gets to the sequencing point. What I’ve seen so far, because everybody is getting palbociclib, whether they get it with letrozole, whether they get it with fulvestrant. So everolimus has been pushed down a little bit.
Adam M. Brufsky, MD: Yeah. That’s kind of where I would use it, probably after.
Joyce A. O’Shaughnessy, MD: And I’m seeing great results in patients who don’t have liver disease, so like the bone-only metastases. They’ve done well with the palbociclib for a while and then you switch them over to exemestane and everolimus, fantastic results but liver not so much.
Hope S. Rugo, MD: But I’ve seen some really excellent. I mean, I kind of look at the scan and go did they compare it to the right one, where I’ve seen shrinkage of liver lesions with everolimus.
Christy A. Russell, MD: I have as well.
Joyce A. O’Shaughnessy, MD: After palbociclib.
Hope S. Rugo, MD: After palbociclib.
Adam M. Brufsky, MD: The problem is we just don’t have any markers. That’s our problem.
Sara A. Hurvitz, MD: We have no data.
Adam M. Brufsky, MD: We have not good data. We have no data. We have no markers. We have nothing to tell us things are going to work and who to select the patients for, that’s the problem. We would love to have some sort of gene, a mutation in some gene that predicts response of everolimus, you know that you do the circulating DNA and suddenly it pops up. You give the woman everolimus.
Joyce A. O’Shaughnessy, MD: We’re going to really need that, I think, yeah.
Adam M. Brufsky, MD: Hopefully, I mean but that’s pie in the sky. I don’t think I’ve seen one yet.
Christy A. Russell, MD: So just so we didn’t ever figure out how to sequence all of our single agent endocrine therapies, we’re not going to be able to figure out how to do these combined therapies.
Hope S. Rugo, MD: And we also have the histone deacetylase inhibitor, entinostat that’s in a randomized phase III trial in a Cooperative Group.
Adam M. Brufsky, MD: Yes, we do, phase III. We have some old school drugs. I remember Joyce, we had a conversation in San Antonio about the return of high-dose estrogen.
Hope S. Rugo, MD: It’s funny and I don’t have a lot of candidates anymore since the advent of everolimus and palbociclib. We kind of run out of endocrine therapy in most of these people but I still use it.
Transcript Edited for Clarity