Perspectives on Systemic Therapy for Breast Cancer - Episode 1
Adam M. Brufsky, MD, PhD, FACP: Hello, and thank you for joining this OncLive® Peer Exchange® titled “Perspectives on Systemic Therapy for Breast Cancer.” As we’ve now headed into 2018, it’s a great time to reflect on the important advances that continue to shape the way we treat our patients. In this OncLive® Peer Exchange® discussion, I am again joined by an expert panel of renowned breast cancer oncologists. Today, we will discuss the research that was presented recently at the San Antonio Breast Cancer Symposium. We’ll review the key abstracts and provide perspective on how the data may influence the future of clinical practice.
I am Dr. Adam Brufsky, and I am a professor of medicine and associate division chief of the Division of Hematology/Oncology at the University of Pittsburgh School of Medicine in Pittsburgh, Pennsylvania.
Participating today on our very distinguished panel are: Dr. Francisco Esteva, Associate Director for Clinical Investigation and director of the Breast Medical Oncology Program at the NYU Langone Perlmutter Cancer Center in New York, New York; Dr. Komal Jhaveri, Attending Physician, Department of Medicine at Memorial Sloan Kettering Cancer Center in New York, New York; Dr. Hope Rugo, Professor of Medicine and director of Breast Cancer Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, California; and finally Dr. Lee Schwartzberg, Executive Director of the West Cancer Center, professor of medicine and chief of the Division of Hematology/Oncology at the University of Tennessee Health Science Center in Memphis, Tennessee. Thank you so much for joining us and let’s begin.
The first really, guys(?), to talk about is hormone receptor-positive breast cancer. And it’s kind of nice that we have a lot of really interesting drugs that we use now, and particularly the CDK4/6 inhibitors in metastatic disease. I think we’ll start I think with ribociclib. Lee, what do you think about ribociclib right now? Where do you think it stands in terms of the other CDK4/6s?
Lee Schwartzberg, MD, FACP: Well, we have three CDK4/6 inhibitors and they all look very effective in treating postmenopausal women in the first or second-line setting in combination with endocrine therapy either with an AI or with fulvestrant. So we have from San Antonio, the MONALEESA-7 study which looked at premenopausal, perimenopausal women who were treated with ovarian function suppression plus an AI or tamoxifen plus ribociclib. And that was a very nice study because that was a segment of patients that we hadn’t yet formally looked at in the clinical trial setting to see if they would get the same benefit. We had it in the later line with fulvestrant in PALOMA-3, but we didn’t have a full study looking at first-line patients who had not been endocrine resistant in the premenopausal women.
And that study showed very similar results to what we’ve been with the other first-line trials, a hazard ratio of about .55 and about a 10 month, 11 month improvement in disease-free survival. So I think the results are incredibly consistent. I think the results across all the first-line trials are incredibly consistent, and I think now we have another option that is formally clinically trial tested for premenopausal women to use ovarian function suppression and an AI.
Adam M. Brufsky, MD, PhD, FACP: So, Komal, is this something new? I mean, aren’t we all doing this anyway in practice? Have you been doing it in practice at Memorial?
Komal Jhaveri, MD, FACP: Absolutely. So I think we did have data, as Lee pointed out, I think in the MONARCH 2 with abemaciclib and fulvestrant and in PALOMA-3 with fulvestrant and palbociclib where we studied subsets of premenopausal women. And, if we looked at the subgroup analyses for benefit within premenopausal and postmenopausal women, both derived equal benefit. But this is the first time this is a dedicated study of over 670 patients for pre and perimenopausal women and the very first I think that also looks at tamoxifen as ..... [cross-talk]
Adam M. Brufsky, MD, PhD, FACP: That’s the big deal. I think tamoxifen is the big deal, right.
Komal Jhaveri, MD, FACP: And so I think it’s encouraging to see another endocrine partner with tamoxifen. Now, one could theoretically say could be looked at tamoxifen with a CDK4/6 inhibitor without ovarian suppression as a combination. But I think our first-line treatment option for premenopausal women has been ovarian function suppression based on the five trials that we’ve studied and the metaanalyses that we have. So I think this was an appropriate treatment arm with tamoxifen.
Hope S. Rugo, MD: I think it’s a nice thing to be able to consider tamoxifen for these patients, but also the other part of it is that a lot of times people think you have to take the ovaries out of these patients. It’s so hard, young women, metastatic cancer, incurable disease. And now we know we don’t have to take the ovaries out. That’s a really big difference, I think, and hopefully it will be incorporated into future trials because I know for my patients, it’s very frustrating for them to understand that they can only participate in the trial if they had their ovaries out rather than getting the injections.
Adam M. Brufsky, MD, PhD, FACP: So, Hope, you wouldn’t give them an injection, you do nothing?
Hope S. Rugo, MD: No, no, no, no, I would do the LHRH agonist. The issue was that the way the trials were set up, you had to have your ovaries out if you were going to participate MONALEESA, PALOMA, MONARCH. And we kept saying but we use GNRH agonists all the time and it works, and this now shows it does work. They saw the same impact. That I thought was really important.
Adam M. Brufsky, MD, PhD, FACP: So let me ask you guys a question. This is kind of parenthetically before we go back to this. We all know, and we teach the Fellows this, right? The first thing you do in a premenopausal woman with metastatic disease, you make them postmenopausal, by and large. Most of us would agree with that?
Komal Jhaveri, MD, FACP: Right.
Hope S. Rugo, MD: And our guidelines ....
Adam M. Brufsky, MD, PhD, FACP: You were kind of shaking your head. You don’t agree with that?
Francisco Esteva, MD, PhD: Well, you can use tamoxifen alone and now with ribociclib you can extend.
Adam M. Brufsky, MD, PhD, FACP: You’d use Tam and ribociclib without LHRH?
Francisco Esteva, MD, PhD: In patients who are with metastatic disease, I think in the palliative setting it’s acceptable to use tamoxifen alone. If you use tamoxifen plus an AI, I mean plus an LHRH agonist, the responses are higher, but there are more side effects. I think it’s still an option if you want to do that with, for example, ribociclib.
Adam M. Brufsky, MD, PhD, FACP: I’m going to push it a little bit further. So you have a woman that you’ve put on an LHRH and it’s a year later. Let’s say maybe she’s on Palbo, maybe she’s on Ribo, and letrozole as well and she progresses. How many of you would do an estrogen level first?
Adam M. Brufsky, MD, PhD, FACP: You have a woman who’s progressing, so you put her on LHRH, Ribo, and letrozole, nice therapy, good therapy, a little tamoxifen and letrozole, either one with LHRH. It’s now a year later. How many of you would do an estrogen level on that woman?
Komal Jhaveri, MD, FACP: I wouldn’t.
Adam M. Brufsky, MD, PhD, FACP: You would not. Would you, Francisco?
Hope S. Rugo, MD: Who would do a what?
Adam M. Brufsky, MD, PhD, FACP: An estrogen level.
Hope S. Rugo, MD: I do them all the time.
Lee Schwartzberg, MD, FACP: I do them all the time and I think this is important.
Adam M. Brufsky, MD, PhD, FACP: Right, and we’re going to get to this a little later when we talk about .....
Hope S. Rugo, MD: And I use the estrogen ring, so I definitely check estrogen.
Adam M. Brufsky, MD, PhD, FACP: That’s a whole other discussion. But, seriously, you would not, why not?
Komal Jhaveri, MD, FACP: I thought you were trying to say whether we need to continue LHRH and that’s where you were going with this. But it sounds like you’re going.
Adam M. Brufsky, MD, PhD, FACP: I’m going to how many are resistant, that’s what I’m asking.
Komal Jhaveri, MD, FACP: Correct, right. So then for that I would definitely want to check and know whether we’re actually suppressing it, especially we’re giving AI with LHRH.
Hope S. Rugo, MD: Yes. It’s less so with tamoxifen.
Komal Jhaveri, MD, FACP: Exactly.
Adam M. Brufsky, MD, PhD, FACP: Our prostates colleagues who give LHRH all the time, maybe it’s different in men and women, I don’t think it is, about 25% of the time it’s not suppressive.
Lee Schwartzberg, MD, FACP: We know that from the adjuvant trials.
Adam M. Brufsky, MD, PhD, FACP: Correct, we’ll talk about in a few minutes, um hmm.
Hope S. Rugo, MD: But we know that in premenopausal women where we’re giving GNRH agonists, that most patients suppress, not 100%, and so you have to check Estradiol. If you don’t check the Estradiol you don’t know what you’re doing if you’re giving an AI. If you’re giving tamoxifen it doesn’t matter so much.
Komal Jhaveri, MD, FACP: About 16% don’t really suppress their Estradiol levels, but in the context of not having any vaginal bleeding, I think sometimes community doctors or other doctors don’t necessarily think it is important to check. But I think you bring up a great point that we should.
Adam M. Brufsky, MD, PhD, FACP: But the bottom line is what I’m trying to say is yes, we don’t take their ovaries out, but what we should be doing especially if you’re going to use the MONALEESA regimen now going forward is you’ve got to be careful about their estrogen level, especially if they progress. Because it will be a year later, some people will progress, we’ll go, oh, they’re resistant to LHRH.
Hope S. Rugo, MD: No, totally agree.
Adam M. Brufsky, MD, PhD, FACP: When it’s just an estrogen issue.
Lee Schwartzberg, MD, FACP: Even if they don’t progress, if you’re using an AI you should check it periodically because especially very young women. So the closer to perimenopausal it’s one thing, the ovarian function is not a strong.
Adam M. Brufsky, MD, PhD, FACP: But we’re going to get into that I think a little later when we talk about adjuvant therapy, but I just wanted to bring that up.
Transcript Edited for Clarity