Triple-Positive Metastatic Breast Cancer

Transcript:Adam M. Brufsky, MD, PhD: Let’s just take a minute and talk a little bit about the treatment of triple-positive disease in the metastatic setting. So, we have a bunch of trials. We have PERTAIN. We have a trial being presented, ALTERNATIVE, actually tomorrow at ASCO. So, we have these trials out. What are people’s go-to regimens now if someone walks in the door with triple-positive disease? Let’s start with you, Kim. What do you usually give them?

Kimberly L. Blackwell, MD: I give them the CLEOPATRA regimen, because I believe in the 15.8 months’ improvement in overall survival. That’s in the setting of a taxane, and in CLEOPATRA it was docetaxel. I’ll utilize that between 4 and 6 cycles, and in the ER-positive setting, I’m very quick to drop out the taxane and add an aromatase inhibitor in. I started someone yesterday on 12 weeks of paclitaxel who was strongly ER-positive. She had a 9-year disease-free interval with asymptomatic lung metastases. You hate to give the chemotherapy component, but I’m still compelled to do some chemotherapy with pertuzumab and trastuzumab. And, in that case, I will use 12 weeks of paclitaxel, see her at week 6, and make certain I’m not giving her neuropathy, because most of these women have already had taxane in the adjuvant setting. And then I see her at week 12 and we withdraw the chemotherapy. We’d usually do the scans at that point and add the endocrine agent.

Adam M. Brufsky, MD, PhD: So, would there be anybody whom you wouldn’t give chemotherapy to, just give endocrine therapy HP to upfront? No chemotherapy?

Kimberly L. Blackwell, MD: If you’re asking me, no, because I think the survival benefits were really proven with some upfront taxane.

Debu Tripathy, MD: Yes. Someone who is a borderline candidate for chemotherapy, maybe, but I agree.

José Baselga, MD, PhD: But you can give chemotherapy in a way that is very well tolerated.

Adam M. Brufsky, MD, PhD: Well, weekly paclitaxel, I agree.

José Baselga, MD, PhD: Weekly paclitaxel, I agree. But I think the approach that Kim is mentioning is the one that we also do at our place. You start with chemotherapy, then, when you begin to have side effects mounting up, you stop and you add the AI. I think the PERTAIN trial…

Adam M. Brufsky, MD, PhD: There’s an arm of that trial without chemotherapy, right?

José Baselga, MD, PhD: Yes, and it shows the combinations of hormone therapy alone without chemotherapy with Herceptin are something that was not being very frequently used, because we had the data from the TAnDEM study that were not very impressive. The study was positive, but the control arm performed very poorly. But now you have the PERTAIN trial in which you have good outcome, so I think the concept of sequential chemotherapy followed by hormonal therapy, keeping pertuzumab and Herceptin, is something that is very appealing.

Adam M. Brufsky, MD, PhD: So, most people sound like they would give chemotherapy regardless—triple-positive, even to some with low-volume disease. That’s interesting, because it’s contrary to what we just talked about a half an hour ago. There’s no visceral crisis here. Why are we giving chemotherapy?

Denise A. Yardley, MD: It’s the label of pertuzumab, too, trying to get it approved.

Adam M. Brufsky, MD, PhD: Sticking with the label. Assume the label was anything you wanted, though. Let’s change it up a little.

Debu Tripathy, MD: Well, HER2-positive disease is intrinsically different. We know that hormonal therapy alone is very ineffective.

Carlos L. Arteaga, MD: There are also the data from NeoSphere, right? That was chemotherapy, HP without chemotherapy. The pathological CR rate—what was it, single digits? That’s a lower burden than any metastatic burden you can think of.

Adam M. Brufsky, MD, PhD: Although PAMELA, which is a trial we could talk about now, was HP, and people who were HER2 enriched had a fairly high pCR rate, did they not?

Carlos L. Arteaga, MD: They were selected.

Adam M. Brufsky, MD, PhD: They were selected because they were HER2 enriched, so that’s the idea.

Debu Tripathy, MD: Yes. There may be a subgroup of patients who don’t need intensive therapy in the early-stage setting, and there are some designs now that are being considered where, if you get a pCR to bio only, you don’t get any more treatment. I don’t consider that standard by any means, because those patients may be at higher risk for recurrence. But there may be a subset, and we have yet to define that.

Kimberly L. Blackwell, MD: Yes. To be clear, we don’t know that.

Adam M. Brufsky, MD, PhD: We don’t know that, right. That’s true.

Kimberly L. Blackwell, MD: That group won’t derive an average survival benefit of close to 16 months.

Debu Tripathy, MD: Right. Even when someone gets what I consider—for example, in NeoSphere, patients get just the taxane and HP and have a pCR rate, but that’s not the complete therapy. I still feel that patients need to get on the back end of that trial. Of course, they got FEC [5-fluorouracil/epirubicin/cyclophosphamide], and I would not withhold that at this point in someone who has had a pCR, although I think in a trial setting we may want to explore which of those patients may do well.

Adam M. Brufsky, MD, PhD: I’ll give an actual case. I’ll tell you, it’s how we do this; it’s a neoadjuvant case. After 3 cycles of TCHP, the surgeon thought the tumor was growing, so he took it out—pCR, 26 years old. What would you do? If you’re a believer in pCR, you would stop, right?

Debu Tripathy, MD: No, I’d complete it.

Adam M. Brufsky, MD, PhD: Continue the chemotherapy. So, we’re basically saying, because of the survival benefit, especially in the metastatic setting, you have to do chemotherapy regardless.

Kimberly L. Blackwell, MD: Yes. I just think when you see survival benefits, you have do it, as much as you hate to do it and you just want to not have to do it.

Adam M. Brufsky, MD, PhD: Right.

José Baselga, MD, PhD: The CLEOPATRA has over 50 months of survival.

Adam M. Brufsky, MD, PhD: It does, I agree with you.

José Baselga, MD, PhD: You cannot argue with these data. I think probably HER2-positive disease is the only setting where we have very strong survival data, right?

Adam M. Brufsky, MD, PhD: We do.

José Baselga, MD, PhD: So, how can you ignore that? It’s very tough.

Adam M. Brufsky, MD, PhD: You can’t.

Kimberly L. Blackwell, MD: Even in the ER-positive early-stage setting, those patients do extremely well. You don’t want to skimp on something that’s pretty much curing the majority of these women.

Transcript Edited for Clarity