HER2+ Breast Cancer: Neratinib Patient Selection



Adam M. Brufsky, MD, PhD: So, we now have neratinib. I think we said pertuzumab, it sounds like we’re not that enthusiastic about the adjuvant use of it.

Joyce A. O’Shaughnessy, MD: In some settings, yes.

Adam M. Brufsky, MD, PhD: If we were using it neoadjuvantly, from what I’m hearing. But what about neratinib? So, the way I personally look at it again is this, basically if people who were not going to have pCRs generally are ER-positive, or triple-positive, and the people who do not have a pCR, maybe are those the ones who are looking at neratinib too adjuvantly?

Michael Gnant, MD: Well, we don’t have it at this moment. But if we had, probably it would be the reverse subset, so that’s the lower risk, the receptor positives based on the data—4.4% for instance, and that’s not trivial.

Adam M. Brufsky, MD, PhD: No, it is not trivial. I agree.

Michael Gnant, MD: So, if it were my sister, I think I would return, and why should I treat my patients less than my sister?

Michael Untch, MD: We have seen the long-term data from all those adjuvant trials with chemotherapy and trastuzumab. You have shown in yesterday’s session also, Hope, that 30% to 40% of the patients with multiple involved lymph nodes, even with the best therapy we have, still have metastases and recurrences. So, these are the patients who definitely need additional therapy. If the patient comes from the surgeon in your country, we are the surgeon ourselves because we do the medical treatment and the surgery. But if it happens, Hope, Joyce, or Adam, that the patient comes from the surgeon too, the patient has 4 or more involved lymph nodes, probably you would advise her to have a double blockade, period.

Adam M. Brufsky, MD, PhD: Absolutely.

Michael Untch, MD: Now, she comes to your office 1 year after finishing trastuzumab adjuvant therapy. She is hormone receptor-positive and you have neratinib available, she’s asking you, “Dr. Brufsky, what can I do?” And you would tell her, “Oh yes, we have this drug, it’s available, we can manage the diarrhea.”

Adam M. Brufsky, MD, PhD: Understand, you’re going to be on round-the-clock loperamide for the first month, but yes. That’s what I would tell people.

Hope S. Rugo, MD: Only the first month, and only some people.

Adam M. Brufsky, MD, PhD: I’ve done that; and I’ve actually told that to somebody.

Michael Untch, MD: And this is what I would do at the moment. But again, if a patient comes with a new diagnosis of HER2-positive disease from the biopsy, she’s T2, she has suspicious lymph nodes in the axilla, then obviously I would give her optimal chemotherapy with double blockade. And she belongs to those 60% to 70% who have a pCR. Basically, this patient is cured.

Adam M. Brufsky, MD, PhD: She’s done, I agree.

Michael Gnant, MD: Let’s hope she’s cured.

Hope S. Rugo, MD: Not all of them.

Joyce A. O’Shaughnessy, MD: ER-positive is not as good of a predictor. It’s just not, even in the HER2-positive.

Adam M. Brufsky, MD, PhD: We should move on to triple-negative, but I’m going to ask a question now. So, that person gets the 6 cycles, or however many cycles in neoadjuvant therapy you give, depending on what part of the world you are in—and even in the United States, it depends on what coast of the country you are in. And you get that you have a pCR, does that person need the Herceptin after?

Michael Untch, MD: My hypothesis is no.

Joyce A. O’Shaughnessy, MD: For ER-negative.

Adam M. Brufsky, MD, PhD: For ER-negative.

Michael Untch, MD: ER-negative, my hypothesis is no.

Michael Gnant, MD: In clinical practice, we still give it.

Adam M. Brufsky, MD, PhD: We still give it. We give 11 more doses.

Michael Gnant, MD: But I think based on the numerics of APHINITY, at least we’re not forced to give double for such a patient.

Adam M. Brufsky, MD, PhD: I agree; we’re not going to give double.

Michael Untch, MD: Adam, we went to the European community 5 years ago with Gunter von Minckwitz and asked for a trial to be financed with this design. Unfortunately, it was refused. So, at the moment, what I’m saying is a hypothesis. In the clinical practice, this patient is still receiving a 6-month adjuvant or postsurgical treatment with trastuzumab, but basically, we don’t know whether this patient needs the treatment or not.

Adam M. Brufsky, MD, PhD: Well, that’s a good point. It’s a great point.

Transcript Edited for Clarity

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