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HER2+ Breast Cancer: Use of Weekly Paclitaxel-Trastuzumab

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:
Let’s just talk a little bit about where we use, each of us—there will be some practice variations—weekly paclitaxel-trastuzumab, which is really an adjuvant regimen, right? So Aditya, how do you actually use it?

Aditya Bardia, MD, MPH: In general, we’ve not used trastuzumab plus paclitaxel in the neoadjuvant setting. In the adjuvant setting we consider it for patients who have T1b or T1c disease. Having said that, if I have someone who’s young, who has T1c disease that’s ER-negative, we’ve also used TCHP [docetaxel, carboplatin, and trastuzumab plus pertuzumab]. T1c is dependent on that specific individual. For T1a in general we’ve not used Taxol plus Herceptin.

Joyce O’Shaughnessy, MD: For T1a?

Aditya Bardia, MD, MPH: I’m not using it.

Joyce O’Shaughnessy, MD: Not using it, you don’t treat in general the T1a M0s.

Aditya Bardia, MD, MPH: T1a M0 is usually, especially ER-positive, endocrine therapy alone.

Joyce O’Shaughnessy, MD: Yes.

Aditya Bardia, MD, MPH: And Taxol/Herceptin is a very good regimen, but there are also potential side effects with neuropathy. We’ve had a couple of patients who had hypersensitivity reaction. So I think you just have to weigh the potential risk of recurrence with the potential absolute benefit you’ll get for the addition of Taxol plus Herceptin.

Joyce O’Shaughnessy, MD: How about you Ruth?

Ruth O'Regan, MD: Exactly the same. As I say, I don’t feel strongly with T1as. I probably would discuss it but probably not do it. Essentially patients with stage I diseases are our T1as. But I do think, as I said, the T1c is going to be a discussion for sure based on this study.

Heather L. McArthur, MD, MPH: Especially if they’re hormone receptor. That’s a group…that I still like. I think it’s a very individual discussion, as you point out, because I certainly would still consider a patient with a 4-mm ER-negative tumor. I don’t have an absolute cutoff in terms of 5 mm is yes to TH [paclitaxel and trastuzumab] and then 4.5 mm is not. So I think you really have to tailor your recommendations to the patient in front of you.

Joyce O’Shaughnessy, MD: The NCCN [National Comprehensive Cancer Network] guidelines really just discourage treatment of T1a disease. They really do. They say, “When you get to T1B now you start thinking about it.” But those are the NCCN guidelines. But as I looked at the HER2-positive and the triple- negative settings, you’re hard pressed to see a difference in outcome in disease-free survival. It’s about 10% for both of them. That’s probably because in some ways it’s hard for the pathologist to actually know what is 5 mm versus 6 mm. Do you know what I mean? There’s going to be a little overlap there.

So yes, I tend to use the weekly paclitaxel-trastuzumab for the T1a, T1b patients unless I’m a little worried that it’s 9 mm or 10 mm and it’s highly proliferative and NRC-negative . I’ll want to get some platinum in there, usually TCH [docetaxel,  carboplatin, trastuzumab]. But I think for the T1c patients, I personally will welcome the opportunity to treat those patients preoperatively because the strong message coming out of the KATHERINE trial is really knowing who needs additional therapy. I’ll welcome the opportunity to give four cycles of TCHP [docetaxel, carboplatin, and trastuzumab plus pertuzumab]. And then if they’re pathologic CR [complete response], just really be done. If they’re clinically node-negative I probably would de-escalate down to the trastuzumab by itself. But how about you guys? Where do you use the weekly paclitaxel-trastuzumab?

Tiffany A. Traina, MD: I think I would really echo really what you’ve been saying. One thing that didn’t come up, and I wish I had an answer for this, was how ,with the definition of what “HER2 positive” is evolving, there are some patients who I think are HER2 positivity by copy number, perhaps with a little bit of a larger tumor. I don’t know if that’s truly going to be such HER2-driven disease, and I might be more comfortable using polychemotherapy rather than relying only the weekly paclitaxel. So I’m not sure how HER2-driven that underlying disease is. I don’t know if anyone else struggles this.

Ruth O'Regan, MD: I think we’ve all really struggled with this and you don’t want to undertreat a triple- negative disease so I don’t tend to use anthracyclines very much, but would be the patient where I wouldn’t consider doing that.

Adam M. Brufsky, MD, PhD: I take a slightly different approach.

Joyce O’Shaughnessy, MD: Go for it Adam.

Adam M. Brufsky, MD, PhD: I think we’re overtreating too many people. I think in the T1a setting, you really have to ask yourself the absolute benefit of the chemotherapy. It’s in the single digits. It’s not huge but I think some patients will want that, some won’t. That’s a discussion of T1a. In T1b especially, triple-positive disease, I think a lot of that could be luminal A.  I think some T1c diseases could be luminal A. I think about 20% of patients are probably luminal A. It probably doesn’t matter what we give them. In fact, some people think you should just give them hormone therapy alone. I think that for T1c and below I will give TH. I think it’s a reasonable therapy. In fact, remember, the APT trial went up to 3 cm, so even above T2.

If they have node positivity once we do their lymph node dissection or sentinel dissection—if someone comes in with a T1c disease, we do the sentinel dissection, and they’re node-positive—they’ll get TCHP, APHINITY. That’s 91%, 92% 5-year DFS [disease-free survival], 4-year DFS. It’s still pretty good. And it’s hard for us to get beyond that. For anything above T2 I would think about neoadjuvant therapy, I agree with you. But don’t you think we’re overtreating the T1Cs by giving them TCHP or ACTHP [trastuzumab and pertuzumab]? I think we’re overtreating them a little bit. This is why this practice variation. There’s no right or wrong answer here.

Ruth O'Regan, MD: It depends on the age of the patient.

Adam M. Brufsky, MD, PhD: Yes, I would buy that.

Joyce O’Shaughnessy, MD: In the adjuvant setting I’ll just do TCH with T1c M0s because we don’t have the level one evidence.

Adam M. Brufsky, MD, PhD: I would use TCHP for node positive disease in adjuvant setting, but I’d do neoadjuvant therapy too, yes.


Transcript Edited for Clarity
 

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Transcript: 

Joyce O’Shaughnessy, MD:
Let’s just talk a little bit about where we use, each of us—there will be some practice variations—weekly paclitaxel-trastuzumab, which is really an adjuvant regimen, right? So Aditya, how do you actually use it?

Aditya Bardia, MD, MPH: In general, we’ve not used trastuzumab plus paclitaxel in the neoadjuvant setting. In the adjuvant setting we consider it for patients who have T1b or T1c disease. Having said that, if I have someone who’s young, who has T1c disease that’s ER-negative, we’ve also used TCHP [docetaxel, carboplatin, and trastuzumab plus pertuzumab]. T1c is dependent on that specific individual. For T1a in general we’ve not used Taxol plus Herceptin.

Joyce O’Shaughnessy, MD: For T1a?

Aditya Bardia, MD, MPH: I’m not using it.

Joyce O’Shaughnessy, MD: Not using it, you don’t treat in general the T1a M0s.

Aditya Bardia, MD, MPH: T1a M0 is usually, especially ER-positive, endocrine therapy alone.

Joyce O’Shaughnessy, MD: Yes.

Aditya Bardia, MD, MPH: And Taxol/Herceptin is a very good regimen, but there are also potential side effects with neuropathy. We’ve had a couple of patients who had hypersensitivity reaction. So I think you just have to weigh the potential risk of recurrence with the potential absolute benefit you’ll get for the addition of Taxol plus Herceptin.

Joyce O’Shaughnessy, MD: How about you Ruth?

Ruth O'Regan, MD: Exactly the same. As I say, I don’t feel strongly with T1as. I probably would discuss it but probably not do it. Essentially patients with stage I diseases are our T1as. But I do think, as I said, the T1c is going to be a discussion for sure based on this study.

Heather L. McArthur, MD, MPH: Especially if they’re hormone receptor. That’s a group…that I still like. I think it’s a very individual discussion, as you point out, because I certainly would still consider a patient with a 4-mm ER-negative tumor. I don’t have an absolute cutoff in terms of 5 mm is yes to TH [paclitaxel and trastuzumab] and then 4.5 mm is not. So I think you really have to tailor your recommendations to the patient in front of you.

Joyce O’Shaughnessy, MD: The NCCN [National Comprehensive Cancer Network] guidelines really just discourage treatment of T1a disease. They really do. They say, “When you get to T1B now you start thinking about it.” But those are the NCCN guidelines. But as I looked at the HER2-positive and the triple- negative settings, you’re hard pressed to see a difference in outcome in disease-free survival. It’s about 10% for both of them. That’s probably because in some ways it’s hard for the pathologist to actually know what is 5 mm versus 6 mm. Do you know what I mean? There’s going to be a little overlap there.

So yes, I tend to use the weekly paclitaxel-trastuzumab for the T1a, T1b patients unless I’m a little worried that it’s 9 mm or 10 mm and it’s highly proliferative and NRC-negative . I’ll want to get some platinum in there, usually TCH [docetaxel,  carboplatin, trastuzumab]. But I think for the T1c patients, I personally will welcome the opportunity to treat those patients preoperatively because the strong message coming out of the KATHERINE trial is really knowing who needs additional therapy. I’ll welcome the opportunity to give four cycles of TCHP [docetaxel, carboplatin, and trastuzumab plus pertuzumab]. And then if they’re pathologic CR [complete response], just really be done. If they’re clinically node-negative I probably would de-escalate down to the trastuzumab by itself. But how about you guys? Where do you use the weekly paclitaxel-trastuzumab?

Tiffany A. Traina, MD: I think I would really echo really what you’ve been saying. One thing that didn’t come up, and I wish I had an answer for this, was how ,with the definition of what “HER2 positive” is evolving, there are some patients who I think are HER2 positivity by copy number, perhaps with a little bit of a larger tumor. I don’t know if that’s truly going to be such HER2-driven disease, and I might be more comfortable using polychemotherapy rather than relying only the weekly paclitaxel. So I’m not sure how HER2-driven that underlying disease is. I don’t know if anyone else struggles this.

Ruth O'Regan, MD: I think we’ve all really struggled with this and you don’t want to undertreat a triple- negative disease so I don’t tend to use anthracyclines very much, but would be the patient where I wouldn’t consider doing that.

Adam M. Brufsky, MD, PhD: I take a slightly different approach.

Joyce O’Shaughnessy, MD: Go for it Adam.

Adam M. Brufsky, MD, PhD: I think we’re overtreating too many people. I think in the T1a setting, you really have to ask yourself the absolute benefit of the chemotherapy. It’s in the single digits. It’s not huge but I think some patients will want that, some won’t. That’s a discussion of T1a. In T1b especially, triple-positive disease, I think a lot of that could be luminal A.  I think some T1c diseases could be luminal A. I think about 20% of patients are probably luminal A. It probably doesn’t matter what we give them. In fact, some people think you should just give them hormone therapy alone. I think that for T1c and below I will give TH. I think it’s a reasonable therapy. In fact, remember, the APT trial went up to 3 cm, so even above T2.

If they have node positivity once we do their lymph node dissection or sentinel dissection—if someone comes in with a T1c disease, we do the sentinel dissection, and they’re node-positive—they’ll get TCHP, APHINITY. That’s 91%, 92% 5-year DFS [disease-free survival], 4-year DFS. It’s still pretty good. And it’s hard for us to get beyond that. For anything above T2 I would think about neoadjuvant therapy, I agree with you. But don’t you think we’re overtreating the T1Cs by giving them TCHP or ACTHP [trastuzumab and pertuzumab]? I think we’re overtreating them a little bit. This is why this practice variation. There’s no right or wrong answer here.

Ruth O'Regan, MD: It depends on the age of the patient.

Adam M. Brufsky, MD, PhD: Yes, I would buy that.

Joyce O’Shaughnessy, MD: In the adjuvant setting I’ll just do TCH with T1c M0s because we don’t have the level one evidence.

Adam M. Brufsky, MD, PhD: I would use TCHP for node positive disease in adjuvant setting, but I’d do neoadjuvant therapy too, yes.


Transcript Edited for Clarity
 
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