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Neoadjuvant Therapy for HER2+ Breast Cancer

Panelists:Adam M. Brufsky, MD, University of Pittsburgh; Sara A. Hurvitz, MD, David Geffen School of Medicine; Joyce A. O'Shaugnessy, MD, Baylor Charles A. Sammons Cancer Center; Hope S. Rugo, MD, University of California; Christy A. Russell, MD, University of Southern California
Published: Monday, Apr 04, 2016


Transcript:

Adam M. Brufsky, MD:
So, before we end this topic, let’s talk a little bit about neoadjuvant and adjuvant HER2 inhibition. I want to talk briefly about the ADAPT study that was presented at ASCO by Nadia Harbeck.

Hope S. Rugo, MD: I think the neoadjuvant setting has been most successful in HER2-positive disease, having led to accelerated approval of pertuzumab as neoadjuvant therapy based on data from two different trials, showing an improvement in pathologic complete response and in a drug which is already approved for advanced disease. So we know that the neoadjuvant setting is kind of a unique area for HER2-positive disease where we see high rates of pathologic complete response, and it has translated in adding trastuzumab or not, based on the original NOAH trial which showed improved survival in those patients. People used it as sort of a training ground. The ADAPT series of trials looked at different subgroups of breast cancer. So they have a triple-negative group, then they have a HER2-positive group, and then HER2-positive/ER-positive group. And this came from the West German Study Group, which is different from the German Breast Group (GBG).

Adam M. Brufsky, MD: You have to be very careful you don’t call it GBG. No, I’ve made that mistake and I will never make it again.

Hope S. Rugo, MD: But they work together a lot.

Adam M. Brufsky, MD: I’m terribly sorry, Nadia.

Hope S. Rugo, MD: But they do work together a lot. But I thought that this series of trials were quite innovative. They’ve actually looked at some really interesting designs. So in HER2-positive disease what they said was, do people who have hormone receptor positive/HER2-positive disease, something we talked about earlier, really need chemotherapy. And if we need to give them chemotherapy, could we give them something kinder and gentler, still chemo, TDM-1. So patients received endocrine therapy and trastuzumab or TDM-1. So the three arms were, just to go over it again – TDM-1, TDM-1 and endocrine therapy, or trastuzumab and endocrine therapy. And what was fascinating was that the patients who received TDM-1, whether or not they received endocrine therapy, had a higher pathologic complete response rate which was quite impressive, actually, for this group of patients. And if you put that into the background of the pathologic CR rate is lower in ER-positive/HER2-positive disease than ER-negative/HER2-positive disease, so we know that. There are late relapses in this patient population, and we’ve always questioned the intensity of treatment. This may be a therapy that’s quite effective in this subset of patients. I thought it was quite intriguing that it didn’t really matter if you gave them endocrine therapy because the endocrine effect is long-term, and it kind of relates to some of the other data we’ve seen in overlapping HER2-targeted therapy with endocrine therapy for longer than a year or for longer term that we’ll talk about next. Because maybe that’s also a critical part of treating these patients in the long-term. Anyway, it’s very well tolerated and not a lot of toxicity and certainly no unexpected toxicities.

Adam M. Brufsky, MD: Before we go to the ExteNET study, I just want to ask one question. There’s a nice trial that the TBCRC did. They are kind of like a small group of phase II investigators.

Hope S. Rugo, MD: ATTEMPT trial.

Adam M. Brufsky, MD: The ATTEMPT trial which is a really cool trial which is using TDM-1 for four doses. Is it four doses?

Hope S. Rugo, MD: No, it’s one year.

Adam M. Brufsky, MD: It’s a one year TDM-1 regimen.

Hope S. Rugo, MD: It’s a lot of TDM-1.

Adam M. Brufsky, MD: It’s a lot of TDM-1.

Hope S. Rugo, MD: According to my patients. Adam M. Brufsky, MD: It’s TDM-1 for a year versus Taxol or paclitaxel and trastuzumab for 12 weeks.

Hope S. Rugo, MD: A 3:1 randomization.

Adam M. Brufsky, MD: 3:1 randomization. So that will be really interesting to see what happens in the trial. For low-risk HER2s now, do you all use the TH for 12 weeks?

Christy A. Russell, MD: Yes.

Hope S. Rugo, MD: APT regimen?

Adam M. Brufsky, MD: APT. They call it APT. I call it TH.

Sara A. Hurvitz, MD: But in the ADAPT study, the interesting thing about it to me is four cycles, right?

Hope S. Rugo, MD: Only four.

Adam M. Brufsky, MD: Only four; that was my point.

Sara A. Hurvitz, MD: And if you compare it again—no-no, cross trial comparison— but you compare it to the four cycles in NeoSphere of THP, the pathologic CR rate in that study in the ER-positives was very low, less than 20%, I think or less than 15% for that group.

Hope S. Rugo, MD: That’s the only thing that makes me suspicious.

Sara A. Hurvitz, MD: It’s very surprising, yeah.

Adam M. Brufsky, MD: I think I’d be excited, not suspicious.

Sara A. Hurvitz, MD: Exactly.

Hope S. Rugo, MD: Well, but, you know, you’re excited; but, again, these are all relatively small trials. What it really means—whether you had a better group of patients— I don’t know. I mean, it is fascinating and I thought the same think Then I thought, well, how can I compare across trials. I just don’t know.

Sara A. Hurvitz, MD: It’s tough.

Christy A. Russell, MD: Well, you have the TRYPHAENA trial, but that’s a lot of chemotherapy.

Adam M. Brufsky, MD: That’s a lot of chemo.

Christy A. Russell, MD: And in the ER-positive patients you are at 50% pathologic complete response rate. And so if you compared TDM-1 in this population versus that, just the toxicity is better.

Adam M. Brufsky, MD: Toxicity is much better.

Hope S. Rugo, MD: That’s a good comparison.

Christy A. Russell, MD: But it is the same complete pathologic complete response rate.

Adam M. Brufsky, MD: But I’m not sure clinically. Would anybody use this clinically now?

Hope S. Rugo, MD: Well, we don’t have it approved.

Adam M. Brufsky, MD: Right.

Joyce A. O’Shaughnessy, MD: We don’t have systemic outcome data.

Christy A. Russell, MD: So the answer is no.

Adam M. Brufsky, MD: Right, that’s my point. So, I mean, I wouldn’t use it right now.

Joyce A. O’Shaughnessy, MD: Yeah, right.

Hope S. Rugo, MD: I think the ATTEMPT trial data is going to be really critical. But it is interesting. If you get TDM-1 versus 12 weeks of weekly paclitaxel and a year of trastuzumab, I don’t know that it’s going to be a clear toxicity benefit for those patients. So our patients who use cold caps don’t lose their hair with weekly paclitaxel at all and then they’re done. They just get trastuzumab. Whereas, the patients who are getting TDM-1 still have some nausea and the counts we’re watching and dose reducing and this and that.
                                                                                                                                                                                                                                                                                                          
Transcript Edited for Transcript
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Transcript:

Adam M. Brufsky, MD:
So, before we end this topic, let’s talk a little bit about neoadjuvant and adjuvant HER2 inhibition. I want to talk briefly about the ADAPT study that was presented at ASCO by Nadia Harbeck.

Hope S. Rugo, MD: I think the neoadjuvant setting has been most successful in HER2-positive disease, having led to accelerated approval of pertuzumab as neoadjuvant therapy based on data from two different trials, showing an improvement in pathologic complete response and in a drug which is already approved for advanced disease. So we know that the neoadjuvant setting is kind of a unique area for HER2-positive disease where we see high rates of pathologic complete response, and it has translated in adding trastuzumab or not, based on the original NOAH trial which showed improved survival in those patients. People used it as sort of a training ground. The ADAPT series of trials looked at different subgroups of breast cancer. So they have a triple-negative group, then they have a HER2-positive group, and then HER2-positive/ER-positive group. And this came from the West German Study Group, which is different from the German Breast Group (GBG).

Adam M. Brufsky, MD: You have to be very careful you don’t call it GBG. No, I’ve made that mistake and I will never make it again.

Hope S. Rugo, MD: But they work together a lot.

Adam M. Brufsky, MD: I’m terribly sorry, Nadia.

Hope S. Rugo, MD: But they do work together a lot. But I thought that this series of trials were quite innovative. They’ve actually looked at some really interesting designs. So in HER2-positive disease what they said was, do people who have hormone receptor positive/HER2-positive disease, something we talked about earlier, really need chemotherapy. And if we need to give them chemotherapy, could we give them something kinder and gentler, still chemo, TDM-1. So patients received endocrine therapy and trastuzumab or TDM-1. So the three arms were, just to go over it again – TDM-1, TDM-1 and endocrine therapy, or trastuzumab and endocrine therapy. And what was fascinating was that the patients who received TDM-1, whether or not they received endocrine therapy, had a higher pathologic complete response rate which was quite impressive, actually, for this group of patients. And if you put that into the background of the pathologic CR rate is lower in ER-positive/HER2-positive disease than ER-negative/HER2-positive disease, so we know that. There are late relapses in this patient population, and we’ve always questioned the intensity of treatment. This may be a therapy that’s quite effective in this subset of patients. I thought it was quite intriguing that it didn’t really matter if you gave them endocrine therapy because the endocrine effect is long-term, and it kind of relates to some of the other data we’ve seen in overlapping HER2-targeted therapy with endocrine therapy for longer than a year or for longer term that we’ll talk about next. Because maybe that’s also a critical part of treating these patients in the long-term. Anyway, it’s very well tolerated and not a lot of toxicity and certainly no unexpected toxicities.

Adam M. Brufsky, MD: Before we go to the ExteNET study, I just want to ask one question. There’s a nice trial that the TBCRC did. They are kind of like a small group of phase II investigators.

Hope S. Rugo, MD: ATTEMPT trial.

Adam M. Brufsky, MD: The ATTEMPT trial which is a really cool trial which is using TDM-1 for four doses. Is it four doses?

Hope S. Rugo, MD: No, it’s one year.

Adam M. Brufsky, MD: It’s a one year TDM-1 regimen.

Hope S. Rugo, MD: It’s a lot of TDM-1.

Adam M. Brufsky, MD: It’s a lot of TDM-1.

Hope S. Rugo, MD: According to my patients. Adam M. Brufsky, MD: It’s TDM-1 for a year versus Taxol or paclitaxel and trastuzumab for 12 weeks.

Hope S. Rugo, MD: A 3:1 randomization.

Adam M. Brufsky, MD: 3:1 randomization. So that will be really interesting to see what happens in the trial. For low-risk HER2s now, do you all use the TH for 12 weeks?

Christy A. Russell, MD: Yes.

Hope S. Rugo, MD: APT regimen?

Adam M. Brufsky, MD: APT. They call it APT. I call it TH.

Sara A. Hurvitz, MD: But in the ADAPT study, the interesting thing about it to me is four cycles, right?

Hope S. Rugo, MD: Only four.

Adam M. Brufsky, MD: Only four; that was my point.

Sara A. Hurvitz, MD: And if you compare it again—no-no, cross trial comparison— but you compare it to the four cycles in NeoSphere of THP, the pathologic CR rate in that study in the ER-positives was very low, less than 20%, I think or less than 15% for that group.

Hope S. Rugo, MD: That’s the only thing that makes me suspicious.

Sara A. Hurvitz, MD: It’s very surprising, yeah.

Adam M. Brufsky, MD: I think I’d be excited, not suspicious.

Sara A. Hurvitz, MD: Exactly.

Hope S. Rugo, MD: Well, but, you know, you’re excited; but, again, these are all relatively small trials. What it really means—whether you had a better group of patients— I don’t know. I mean, it is fascinating and I thought the same think Then I thought, well, how can I compare across trials. I just don’t know.

Sara A. Hurvitz, MD: It’s tough.

Christy A. Russell, MD: Well, you have the TRYPHAENA trial, but that’s a lot of chemotherapy.

Adam M. Brufsky, MD: That’s a lot of chemo.

Christy A. Russell, MD: And in the ER-positive patients you are at 50% pathologic complete response rate. And so if you compared TDM-1 in this population versus that, just the toxicity is better.

Adam M. Brufsky, MD: Toxicity is much better.

Hope S. Rugo, MD: That’s a good comparison.

Christy A. Russell, MD: But it is the same complete pathologic complete response rate.

Adam M. Brufsky, MD: But I’m not sure clinically. Would anybody use this clinically now?

Hope S. Rugo, MD: Well, we don’t have it approved.

Adam M. Brufsky, MD: Right.

Joyce A. O’Shaughnessy, MD: We don’t have systemic outcome data.

Christy A. Russell, MD: So the answer is no.

Adam M. Brufsky, MD: Right, that’s my point. So, I mean, I wouldn’t use it right now.

Joyce A. O’Shaughnessy, MD: Yeah, right.

Hope S. Rugo, MD: I think the ATTEMPT trial data is going to be really critical. But it is interesting. If you get TDM-1 versus 12 weeks of weekly paclitaxel and a year of trastuzumab, I don’t know that it’s going to be a clear toxicity benefit for those patients. So our patients who use cold caps don’t lose their hair with weekly paclitaxel at all and then they’re done. They just get trastuzumab. Whereas, the patients who are getting TDM-1 still have some nausea and the counts we’re watching and dose reducing and this and that.
                                                                                                                                                                                                                                                                                                          
Transcript Edited for Transcript
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