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Moving CDK4/6 Inhibition to HER2+ Breast Cancer

Panelists: Joyce O Shaughnessy, MD, Baylor-Sammons Cancer Center; Aditya Bardia, MD, MPH, Massachusetts General Hospital; Adan M. Brufsky, MD, PhD, Comprehensive Breast Cancer Center; Heather L. McArthur, MD, MPH, Cedars-Sinai Medical Center; Ruth O Regan, MD, University of Wisconsin Carbone Cancer Center; Tiffany A. Traina, MD, Memorial Sloan Kettering Cancer Center
Published: Wednesday, Jan 30, 2019



Transcript:

Joyce O’Shaughnessy, MD:
We heard about the PATINA trial. So, I think that’s bringing the CDK4/6 inhibitors into the HER2-positive setting, is that right? Can you say a few words about that?

Ruth O’Regan, MD: Yes. There are a couple of trials that are looking at adding in CDK4/6 inhibitors in the ER [estrogen receptor]–positive/HER2-positive metastatic setting. So, PATINA is one with palbociclib, so patients have induction treatment, and then they get randomized to…standard anti-HER2 therapy with endocrine therapy with or without palbociclib. And then neoMONARCH, which I think has been open a little bit longer, has a pretty similar design using abemaciclib in that setting. If you look at PERTAIN, I think the bar is quite high for that. I’m always surprised by that. That study showed that the progression-free survival in the trastuzumab endocrine therapy arm is much longer than what we’ve seen in prior studies, which I’ve never been able to explain. So I think it’s going to be very interesting, but there are certainly preclinical data suggesting that the CDK inhibitors should work in HER2-positive disease.

Joyce O’Shaughnessy, MD: PATINA is an ongoing trial at this point.

Ruth O’Regan, MD: Correct.

Joyce O’Shaughnessy, MD: We don’t have data yet for both trials.

Ruth O’Regan, MD: We have data from neither of them at this point.

Adam M. Brufsky, MD, PhD: I’ve heard the accrual was not great on that study. Do you guys know anything about that?

Aditya Bardia, MD, MPH: In general, we are doing so well in the neoadjuvant, adjuvant setting.

Joyce O’Shaughnessy, MD: Yes. Most of them are de novo metastatic.

Adam M. Brufsky, MD, PhD: Right.

Joyce O’Shaughnessy, MD: But we do tend to use—let’s say, de novo metastatic—a CLEOPATRA-like regimen, stop the chemotherapy, keep going with trastuzumab and pertuzumab, and then add endocrine therapy, usually as per the PERTAIN trial.

Ruth O’Regan, MD: But in the PERTAIN trial, even in the group of patients who didn’t get induction chemotherapy, their progression-free survival was very long, much longer than what we had seen before. So I don’t know if anyone can explain that.

Adam M. Brufsky, MD, PhD: Is it selection, maybe?

Ruth O’Regan, MD: But why would it be so different? I just don’t really understand.

Adam M. Brufsky, MD, PhD: Good point.

Joyce O’Shaughnessy, MD: But that was with pertuzumab, trastuzumab.

Ruth O’Regan, MD: But even in the control arm, progression-free survival was 15 months. Remember in the older study, it was like 3 months or something.

Adam M. Brufsky, MD, PhD: And the analogy was TAnDEM, right? That was in the control arm, TAnDEM, right?

Joyce O’Shaughnessy, MD: Yes, yes. So that’s going to be interesting to see. It ought to be, hopefully, tolerable, because if we could make that truly a chronic disease, that would be obviously cool, because one mechanism of escape—in the preclinical literature that I’ve looked at from CDK4/6—involves how anything upstream from that can get upregulated. And, if you don’t have FGFR1 or something like that, you can upregulate. The HER family can be upregulated, so it makes sense to block that, too. We could really clamp things down. It’s great that those trials are ongoing in the metastatic setting.

Heather L. McArthur, MD, MPH: And I would make a plug just because it’s my favorite topic.

Adam M. Brufsky, MD, PhD: Immunotherapy? We’re going to talk about it.

Heather L. McArthur, MD, MPH: The CDK4/6 inhibitors can be immunogenic, and there are some pretty compelling preclinical data and some clinical data supporting checkpoint blockade combinations with CDK4/6 inhibitors.

Joyce O’Shaughnessy, MD: Right, which are ongoing in the metastatic setting.

Transcript edited for clarity.
 

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Transcript:

Joyce O’Shaughnessy, MD:
We heard about the PATINA trial. So, I think that’s bringing the CDK4/6 inhibitors into the HER2-positive setting, is that right? Can you say a few words about that?

Ruth O’Regan, MD: Yes. There are a couple of trials that are looking at adding in CDK4/6 inhibitors in the ER [estrogen receptor]–positive/HER2-positive metastatic setting. So, PATINA is one with palbociclib, so patients have induction treatment, and then they get randomized to…standard anti-HER2 therapy with endocrine therapy with or without palbociclib. And then neoMONARCH, which I think has been open a little bit longer, has a pretty similar design using abemaciclib in that setting. If you look at PERTAIN, I think the bar is quite high for that. I’m always surprised by that. That study showed that the progression-free survival in the trastuzumab endocrine therapy arm is much longer than what we’ve seen in prior studies, which I’ve never been able to explain. So I think it’s going to be very interesting, but there are certainly preclinical data suggesting that the CDK inhibitors should work in HER2-positive disease.

Joyce O’Shaughnessy, MD: PATINA is an ongoing trial at this point.

Ruth O’Regan, MD: Correct.

Joyce O’Shaughnessy, MD: We don’t have data yet for both trials.

Ruth O’Regan, MD: We have data from neither of them at this point.

Adam M. Brufsky, MD, PhD: I’ve heard the accrual was not great on that study. Do you guys know anything about that?

Aditya Bardia, MD, MPH: In general, we are doing so well in the neoadjuvant, adjuvant setting.

Joyce O’Shaughnessy, MD: Yes. Most of them are de novo metastatic.

Adam M. Brufsky, MD, PhD: Right.

Joyce O’Shaughnessy, MD: But we do tend to use—let’s say, de novo metastatic—a CLEOPATRA-like regimen, stop the chemotherapy, keep going with trastuzumab and pertuzumab, and then add endocrine therapy, usually as per the PERTAIN trial.

Ruth O’Regan, MD: But in the PERTAIN trial, even in the group of patients who didn’t get induction chemotherapy, their progression-free survival was very long, much longer than what we had seen before. So I don’t know if anyone can explain that.

Adam M. Brufsky, MD, PhD: Is it selection, maybe?

Ruth O’Regan, MD: But why would it be so different? I just don’t really understand.

Adam M. Brufsky, MD, PhD: Good point.

Joyce O’Shaughnessy, MD: But that was with pertuzumab, trastuzumab.

Ruth O’Regan, MD: But even in the control arm, progression-free survival was 15 months. Remember in the older study, it was like 3 months or something.

Adam M. Brufsky, MD, PhD: And the analogy was TAnDEM, right? That was in the control arm, TAnDEM, right?

Joyce O’Shaughnessy, MD: Yes, yes. So that’s going to be interesting to see. It ought to be, hopefully, tolerable, because if we could make that truly a chronic disease, that would be obviously cool, because one mechanism of escape—in the preclinical literature that I’ve looked at from CDK4/6—involves how anything upstream from that can get upregulated. And, if you don’t have FGFR1 or something like that, you can upregulate. The HER family can be upregulated, so it makes sense to block that, too. We could really clamp things down. It’s great that those trials are ongoing in the metastatic setting.

Heather L. McArthur, MD, MPH: And I would make a plug just because it’s my favorite topic.

Adam M. Brufsky, MD, PhD: Immunotherapy? We’re going to talk about it.

Heather L. McArthur, MD, MPH: The CDK4/6 inhibitors can be immunogenic, and there are some pretty compelling preclinical data and some clinical data supporting checkpoint blockade combinations with CDK4/6 inhibitors.

Joyce O’Shaughnessy, MD: Right, which are ongoing in the metastatic setting.

Transcript edited for clarity.
 
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