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Pathologic Complete Response in 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: Tuesday, Jan 15, 2019



Transcript: 

Joyce O’Shaughnessy, MD:
We’re placing a lot on how the pathologic complete response is a really, really important indicator of outcome. How confident are we that pathologic CR really does mean patients are going to perform exceptionally well, with disease-free survival of 95% or even more. Your group brought some data to the 2018 San Antonio Breast Cancer Symposium, didn’t they do that?

Aditya Bardia, MD, MPH: We had a followup to the FDA meta-analysis. A few years ago the FDA did a meta-analysis of 12 studies, and they demonstrated that if you have a PCR, you have better outcomes as compared to no PCR. We did a meta-analysis of 52 neoadjuvant studies where we looked at the association between PCR and outcomes. And essentially for patients who had a PCR, the disease-free survival overall was 88%, and for those who didn’t have a PCR, the disease-free survival was 67%.

So there was a clear difference between those who had a PCR versus no PCR with a hazard ratio
of about 0.3. So it is a strong prognostic factor. But if you have a PCR it doesn’t mean that you’ll have 100% disease-free survival. So there are still some patients who despite having a PCR will have recurrence. And the question is, in those who have a PCR can you add something to move that 88% to 95% or 98%? And that’s something that we don’t know, and that’s a challenge in the clinic when you have someone with a PCR. They have a better prognosis but it’s not 100%. And maybe with the addition of some additional therapy, you can move that needle.

Joyce O’Shaughnessy, MD: And endocrine therapy would help certainly if you’re ER-positive. But the
88%, was that in HER2-positive disease?

Aditya Bardia, MD, MPH: This was all-comers.

Adam M. Brufsky, MD, PhD: All-comers, that’s a little bit different.

Joyce O’Shaughnessy, MD: So probably higher in the HER2-positive patients.

Aditya Bardia, MD, MPH: Absolutely.

Joyce O’Shaughnessy, MD: Because the I-SPY 2 data that Doug Yee, MD presented at ASCO American Society of Clinical Oncology Annual Meeting, having accumulated a rather large number of many hundreds of patients, were really interesting. Because remember, to be to be on I-SPY 2, you had to be ER positive HER2 negative, and you’d have to be MammaPrint high risk.

So we’re not talking luminal A, we’re talking luminal B, HER2-positive and triple-negative disease. And it was fascinating that if you got pathologic CR, you were near 94%, 95% event-free survival, you know? And I think their followup was not terribly long. I think it may be even in the 4-year range or something like that, but it was really interesting that it was really uniform across subsets. It’s got to be real hard to improve upon that. But endocrine therapy should really help. So it certainly is encouraging now that pathologic CR is a very reasonable thing to aim for. We are using trastuzumab in the high-risk patients, preoperatively. These patients will mostly for the most part get trastuzumab. Everybody’s comfortable extrapolating from the KATHERINE trial.

Tiffany A. Traina, MD: Right, with about 300 patients.

Joyce O’Shaughnessy, MD: Yes, and the point estimate was just the same in those patients.

Tiffany A. Traina, MD: Right, a 0.54 hazard ratio.

Ruth O'Regan, MD: We might have had a higher pathologic CR rate, but I don’t know why that would
influence the effectiveness of T-DM1 afterwards.

Joyce O’Shaughnessy, MD: Because it’s got to be the non–cross-resistance of the payload. It’s got to be
the maytansine that’s making the difference, right?

Tiffany A. Traina, MD: It may actually be even better in that group. Who knows?

Heather L. McArthur, MD, MPH: Good research questions.

Joyce O’Shaughnessy, MD: Yes. It would be great if it helped the brain, the T-DM1. The metastatic data are just case series. It’s not prospective phase II trials but the case series really show that up to 50% of patients can get responses in the brain with T-DM1 in metastatic setting. So hope springs eternal on that one, and I think further followup of the KATHERINE may give us some insights in that regard.


Transcript Edited for Clarity

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Transcript: 

Joyce O’Shaughnessy, MD:
We’re placing a lot on how the pathologic complete response is a really, really important indicator of outcome. How confident are we that pathologic CR really does mean patients are going to perform exceptionally well, with disease-free survival of 95% or even more. Your group brought some data to the 2018 San Antonio Breast Cancer Symposium, didn’t they do that?

Aditya Bardia, MD, MPH: We had a followup to the FDA meta-analysis. A few years ago the FDA did a meta-analysis of 12 studies, and they demonstrated that if you have a PCR, you have better outcomes as compared to no PCR. We did a meta-analysis of 52 neoadjuvant studies where we looked at the association between PCR and outcomes. And essentially for patients who had a PCR, the disease-free survival overall was 88%, and for those who didn’t have a PCR, the disease-free survival was 67%.

So there was a clear difference between those who had a PCR versus no PCR with a hazard ratio
of about 0.3. So it is a strong prognostic factor. But if you have a PCR it doesn’t mean that you’ll have 100% disease-free survival. So there are still some patients who despite having a PCR will have recurrence. And the question is, in those who have a PCR can you add something to move that 88% to 95% or 98%? And that’s something that we don’t know, and that’s a challenge in the clinic when you have someone with a PCR. They have a better prognosis but it’s not 100%. And maybe with the addition of some additional therapy, you can move that needle.

Joyce O’Shaughnessy, MD: And endocrine therapy would help certainly if you’re ER-positive. But the
88%, was that in HER2-positive disease?

Aditya Bardia, MD, MPH: This was all-comers.

Adam M. Brufsky, MD, PhD: All-comers, that’s a little bit different.

Joyce O’Shaughnessy, MD: So probably higher in the HER2-positive patients.

Aditya Bardia, MD, MPH: Absolutely.

Joyce O’Shaughnessy, MD: Because the I-SPY 2 data that Doug Yee, MD presented at ASCO American Society of Clinical Oncology Annual Meeting, having accumulated a rather large number of many hundreds of patients, were really interesting. Because remember, to be to be on I-SPY 2, you had to be ER positive HER2 negative, and you’d have to be MammaPrint high risk.

So we’re not talking luminal A, we’re talking luminal B, HER2-positive and triple-negative disease. And it was fascinating that if you got pathologic CR, you were near 94%, 95% event-free survival, you know? And I think their followup was not terribly long. I think it may be even in the 4-year range or something like that, but it was really interesting that it was really uniform across subsets. It’s got to be real hard to improve upon that. But endocrine therapy should really help. So it certainly is encouraging now that pathologic CR is a very reasonable thing to aim for. We are using trastuzumab in the high-risk patients, preoperatively. These patients will mostly for the most part get trastuzumab. Everybody’s comfortable extrapolating from the KATHERINE trial.

Tiffany A. Traina, MD: Right, with about 300 patients.

Joyce O’Shaughnessy, MD: Yes, and the point estimate was just the same in those patients.

Tiffany A. Traina, MD: Right, a 0.54 hazard ratio.

Ruth O'Regan, MD: We might have had a higher pathologic CR rate, but I don’t know why that would
influence the effectiveness of T-DM1 afterwards.

Joyce O’Shaughnessy, MD: Because it’s got to be the non–cross-resistance of the payload. It’s got to be
the maytansine that’s making the difference, right?

Tiffany A. Traina, MD: It may actually be even better in that group. Who knows?

Heather L. McArthur, MD, MPH: Good research questions.

Joyce O’Shaughnessy, MD: Yes. It would be great if it helped the brain, the T-DM1. The metastatic data are just case series. It’s not prospective phase II trials but the case series really show that up to 50% of patients can get responses in the brain with T-DM1 in metastatic setting. So hope springs eternal on that one, and I think further followup of the KATHERINE may give us some insights in that regard.


Transcript Edited for Clarity
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