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Adjuvant Therapy for High-Risk HER2+ Breast Cancer

Panelists: Adam M. Brufsky, MD, PhD, University of Pittsburgh Cancer Institute; Carlos L. Arteaga, MD, Vanderbilt University; Jose Baselga, MD, PhD, Memorial Sloan Kettering Cancer Center; Kimberly Blackwell, MD, Duke Cancer Institute; Debu Tripathy, MD, University of Texas MD Anderson Cancer Center; Denise A. Yardley, MD, Sarah Cannon Research Institute; Hope S. Rugo, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Published: Tuesday, Jul 11, 2017



Transcript:

Hope S. Rugo, MD:
Now, we have 2 adjuvant therapies that have been studied in phase III trials: pertuzumab, of course as upfront therapy, and neratinib, as an extended adjuvant therapy. What’s interesting is that on subset analysis of the trials, it looks like different subsets benefit. So, pertuzumab seems to benefit patients who have node-positive ER-negative disease. At least you know that if you took your higher risk patients with ER-negative disease, that’s where you’re going to get your biggest bang for the buck with pertuzumab.

In contrast, neratinib had its biggest bang for the buck in higher risk patients with ER-positive disease in subset analysis. So, it’s my expectation that that’s exactly what we’re going to do moving forward—again, with the caveat that we don’t really know how long we need to treat patients for. We don’t know if you need to continue pertuzumab for a whole year, and we certainly want to start neratinib as close to the end of the first year of trastuzumab- and/or pertuzumab-based therapy as possible. It does seem to me that patients in the APHINITY trial overall did very, very well. And so, if you take a low-risk population, with a little over almost 4 years of follow-up, those patients are going to overall do well. When we’re adding new drugs, we do want to select the patients who have a higher risk of recurrence and understand, with all the caveats of subsets, that it does appear these agents work differently in different subsets of breast cancer.

I think it’s really important for us to control diarrhea when we are giving pertuzumab to patients—who are also getting docetaxel and carboplatin—to make patients aware up front, and to prophylax. For patients who are receiving neratinib, the prophylaxis is critical. Everybody should receive prophylaxis. The optimal prophylactic regimen is still being determined.

I think that the neratinib area, the whole incorporation of neratinib into our treatments, is going to be interesting. We are going to see results in the not terribly distant future from a trial called NALA, which is looking at lapatinib and capecitabine versus neratinib and capecitabine. It’s the best comparison of neratinib to a standard-approved regimen in terms of a phase III trial that exists. The other trials were comparing apples and oranges in a way.

So, it’ll be interesting to see what happens. Of course, there’s prophylaxis for diarrhea, and the understanding is much better about how to manage diarrhea, and both of the oral tyrosine kinase inhibitors cause at least some degree of it—lapatinib less than neratinib. I think those data will be really helpful for us in understanding how to use neratinib in the metastatic setting. The least amount of prophylaxis you should do with neratinib is the loperamide up front, and what you do is gradually tapper it down.

We have generally prophylaxed for the first 2 months in that control trial, but that beginning is critical. You really want to get patients prophylaxed up front, because if they have terrible diarrhea the first day, they’re going to be very discouraged. So, you help people to understand that the diarrhea occurs early. If we control it early, we can start getting rid of some of the prophylaxis over time. But you’re always going to have to be aware that it’s a risk. It may be induced by diet, having a viral infection, or something like that. So, we do want to balance that out.

I think that education, on part of providers and the patients, is going to manage this reasonably well. There will always be a patient who can’t tolerate an agent. In that situation, where you’ve used prophylaxis and the patient can’t manage the drug for whatever reasons, you do your best. But most patients will be able to tolerate the medication with this approach.

Transcript Edited for Clarity

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Transcript:

Hope S. Rugo, MD:
Now, we have 2 adjuvant therapies that have been studied in phase III trials: pertuzumab, of course as upfront therapy, and neratinib, as an extended adjuvant therapy. What’s interesting is that on subset analysis of the trials, it looks like different subsets benefit. So, pertuzumab seems to benefit patients who have node-positive ER-negative disease. At least you know that if you took your higher risk patients with ER-negative disease, that’s where you’re going to get your biggest bang for the buck with pertuzumab.

In contrast, neratinib had its biggest bang for the buck in higher risk patients with ER-positive disease in subset analysis. So, it’s my expectation that that’s exactly what we’re going to do moving forward—again, with the caveat that we don’t really know how long we need to treat patients for. We don’t know if you need to continue pertuzumab for a whole year, and we certainly want to start neratinib as close to the end of the first year of trastuzumab- and/or pertuzumab-based therapy as possible. It does seem to me that patients in the APHINITY trial overall did very, very well. And so, if you take a low-risk population, with a little over almost 4 years of follow-up, those patients are going to overall do well. When we’re adding new drugs, we do want to select the patients who have a higher risk of recurrence and understand, with all the caveats of subsets, that it does appear these agents work differently in different subsets of breast cancer.

I think it’s really important for us to control diarrhea when we are giving pertuzumab to patients—who are also getting docetaxel and carboplatin—to make patients aware up front, and to prophylax. For patients who are receiving neratinib, the prophylaxis is critical. Everybody should receive prophylaxis. The optimal prophylactic regimen is still being determined.

I think that the neratinib area, the whole incorporation of neratinib into our treatments, is going to be interesting. We are going to see results in the not terribly distant future from a trial called NALA, which is looking at lapatinib and capecitabine versus neratinib and capecitabine. It’s the best comparison of neratinib to a standard-approved regimen in terms of a phase III trial that exists. The other trials were comparing apples and oranges in a way.

So, it’ll be interesting to see what happens. Of course, there’s prophylaxis for diarrhea, and the understanding is much better about how to manage diarrhea, and both of the oral tyrosine kinase inhibitors cause at least some degree of it—lapatinib less than neratinib. I think those data will be really helpful for us in understanding how to use neratinib in the metastatic setting. The least amount of prophylaxis you should do with neratinib is the loperamide up front, and what you do is gradually tapper it down.

We have generally prophylaxed for the first 2 months in that control trial, but that beginning is critical. You really want to get patients prophylaxed up front, because if they have terrible diarrhea the first day, they’re going to be very discouraged. So, you help people to understand that the diarrhea occurs early. If we control it early, we can start getting rid of some of the prophylaxis over time. But you’re always going to have to be aware that it’s a risk. It may be induced by diet, having a viral infection, or something like that. So, we do want to balance that out.

I think that education, on part of providers and the patients, is going to manage this reasonably well. There will always be a patient who can’t tolerate an agent. In that situation, where you’ve used prophylaxis and the patient can’t manage the drug for whatever reasons, you do your best. But most patients will be able to tolerate the medication with this approach.

Transcript Edited for Clarity
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TitleExpiration DateCME Credits
Clinical Vignette Series: 34th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow®Feb 28, 20182.0
34th Annual Miami Breast Cancer Conference® Clinical Case Vignette Series™May 25, 20182.0
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