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Neoadjuvant T-DM1 in HER2+ Early Breast Cancer

Panelists: Adam M. Brufsky, MD, University of Pittsburgh Cancer Institute; Ahmad Awada, MD, PhD, Jules Bordet Institute; Wolfgang J. Janni, MD, PhD, University of Ulm; Hope S. Rugo, MD, UCSF Helen Diller Family Comprehensive Cancer Center; Michael Untch, MD, Helios Klinikum Berlin-Buch
Published Online: Tuesday, Dec 06, 2016



Transcript:

Adam M. Brufsky, MD, PhD:
I’d like to ask a little bit about T-DM1 in the adjuvant/neoadjuvant setting. I think it’s a drug that we had a lot of hopes for, based on the second-line metastatic data that we’ll talk about briefly in a few minutes. But I think in the first-line setting and in the adjuvant/neoadjuvant setting, I don’t think it’s lived up to expectations. Let’s start with Hope. You guys did the I-SPY trial of T-DM1 and pertuzumab. Where do you think this is going, T-DM1?

Hope S. Rugo, MD: It’s actually really interesting. There are three different data sets, and you have to look at them in relationship to MARIANNE, the first-line metastatic trial. It appears that adding pertuzumab to T-DM1 doesn’t necessarily help. We saw that in MARIANNE, where T-DM1, T-DM1/pertuzumab, and the trastuzumab/taxane arms were all similar in terms of PFS. In the neoadjuvant setting, T-DM1 and pertuzumab were inferior to so-called TCHP, the standard regimen of a taxane/carboplatin, and the double antibodies in the KRISTINE trial. In our study, I-SPY, which looks as an adaptively randomized design, you look at estimated pCRs. The T-DM1 plus pertuzumab followed by an anthracycline arm was superior to a taxane plus trastuzumab followed by an anthracycline arm. That may be because we gave double antibodies as opposed to a single antibody; it’s not clear. But I do think that that T-DM1 plus pertuzumab combination will not be pursued. T-DM1 itself may be quite good because we saw in the ADAPT HER2 trial that T-DM1 by itself—we didn’t even have to add the endocrine therapy—resulted in a 40% pathologic CR rate if you just gave four doses to ER+, HER2+ breast cancer, which I thought was very impressive. It’s certainly not dead, and we have the ATEMPT trial, which is nearing completion, actually, maybe at the end of this month.

Adam M. Brufsky, MD, PhD: Next week.

Hope S. Rugo, MD: Oh, yes. I knew it was October. We were both participating in that trial, which randomizes 3:1 to a year of T-DM1 versus the APT so-called regimen, 12 weeks of paclitaxel, and a year of trastuzumab. I still remain up in the air about this because I think a year of every-3-week T-DM1 may be harder for many patients than the APT regimen.

Adam M. Brufsky, MD, PhD: So, let me ask you a question, for our European colleagues, about ATEMPT and about using a taxane/trastuzumab for 12 weeks as therapy for early stage breast cancer. Is that used in Europe? Michael, do you use it?

Michael Untch, MD: Can I start?

Adam M. Brufsky, MD, PhD: Yes, please.

Michael Untch, MD: Number 1, the Tolaney data, which had been published, I think, last year…

Adam M. Brufsky, MD, PhD: About a year-and-a-half ago, yes.

Michael Untch, MD: The data are reassuring us that there is a patient population—like the node-negatives with small tumor burden, small tumors, maybe the patients older than 60 and so on who still are HER2+—that still needs chemotherapy and trastuzumab. But maybe with additional cardiac risks, or obesity, or diabetes and so on, those are the patients in which when we talk with them, we think, “Well, we don’t like to give them the full dose and the full anthracycline cycles and so on.” So, these data are very reassuring that we have an excellent disease-free survival by 12 weeks of weekly paclitaxel with the addition of trastuzumab. Actually, we entered this type of therapy in our national guideline in the year 2016. So, we do it. We use it.

Adam M. Brufsky, MD, PhD: Is Brussels the same?

Ahmad Awada, MD, PhD: Exactly the same.

Transcript Edited for Clarity

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Transcript:

Adam M. Brufsky, MD, PhD:
I’d like to ask a little bit about T-DM1 in the adjuvant/neoadjuvant setting. I think it’s a drug that we had a lot of hopes for, based on the second-line metastatic data that we’ll talk about briefly in a few minutes. But I think in the first-line setting and in the adjuvant/neoadjuvant setting, I don’t think it’s lived up to expectations. Let’s start with Hope. You guys did the I-SPY trial of T-DM1 and pertuzumab. Where do you think this is going, T-DM1?

Hope S. Rugo, MD: It’s actually really interesting. There are three different data sets, and you have to look at them in relationship to MARIANNE, the first-line metastatic trial. It appears that adding pertuzumab to T-DM1 doesn’t necessarily help. We saw that in MARIANNE, where T-DM1, T-DM1/pertuzumab, and the trastuzumab/taxane arms were all similar in terms of PFS. In the neoadjuvant setting, T-DM1 and pertuzumab were inferior to so-called TCHP, the standard regimen of a taxane/carboplatin, and the double antibodies in the KRISTINE trial. In our study, I-SPY, which looks as an adaptively randomized design, you look at estimated pCRs. The T-DM1 plus pertuzumab followed by an anthracycline arm was superior to a taxane plus trastuzumab followed by an anthracycline arm. That may be because we gave double antibodies as opposed to a single antibody; it’s not clear. But I do think that that T-DM1 plus pertuzumab combination will not be pursued. T-DM1 itself may be quite good because we saw in the ADAPT HER2 trial that T-DM1 by itself—we didn’t even have to add the endocrine therapy—resulted in a 40% pathologic CR rate if you just gave four doses to ER+, HER2+ breast cancer, which I thought was very impressive. It’s certainly not dead, and we have the ATEMPT trial, which is nearing completion, actually, maybe at the end of this month.

Adam M. Brufsky, MD, PhD: Next week.

Hope S. Rugo, MD: Oh, yes. I knew it was October. We were both participating in that trial, which randomizes 3:1 to a year of T-DM1 versus the APT so-called regimen, 12 weeks of paclitaxel, and a year of trastuzumab. I still remain up in the air about this because I think a year of every-3-week T-DM1 may be harder for many patients than the APT regimen.

Adam M. Brufsky, MD, PhD: So, let me ask you a question, for our European colleagues, about ATEMPT and about using a taxane/trastuzumab for 12 weeks as therapy for early stage breast cancer. Is that used in Europe? Michael, do you use it?

Michael Untch, MD: Can I start?

Adam M. Brufsky, MD, PhD: Yes, please.

Michael Untch, MD: Number 1, the Tolaney data, which had been published, I think, last year…

Adam M. Brufsky, MD, PhD: About a year-and-a-half ago, yes.

Michael Untch, MD: The data are reassuring us that there is a patient population—like the node-negatives with small tumor burden, small tumors, maybe the patients older than 60 and so on who still are HER2+—that still needs chemotherapy and trastuzumab. But maybe with additional cardiac risks, or obesity, or diabetes and so on, those are the patients in which when we talk with them, we think, “Well, we don’t like to give them the full dose and the full anthracycline cycles and so on.” So, these data are very reassuring that we have an excellent disease-free survival by 12 weeks of weekly paclitaxel with the addition of trastuzumab. Actually, we entered this type of therapy in our national guideline in the year 2016. So, we do it. We use it.

Adam M. Brufsky, MD, PhD: Is Brussels the same?

Ahmad Awada, MD, PhD: Exactly the same.

Transcript Edited for Clarity
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