Making Sense of Adjuvant Therapy in HER2+ Breast Cancer

Transcript:

Adam M. Brufsky, MD, PhD: What is everybody going to do now with pertuzumab in the adjuvant setting? Are we going to give pertuzumab and T-DM1 [trastuzumab emtansine]? Or are we just going to do TCHP [docetaxel/carboplatin/trastuzumab/pertuzumab] or AC-THP [doxorubicin/cyclophosphamide/paclitaxel/trastuzumab/pertuzumab]. If there’s no PCR [pathologic complete response], will we give T-DM1 and no pertuzumab? What are we going to do?

Heather L. McArthur, MD, MPH: It’s the latter.

Adam M. Brufsky, MD, PhD: So the latter, just T-DM1, no pertuzumab?

Heather L. McArthur, MD, MPH: Correct.

Adam M. Brufsky, MD, PhD: We’re exchanging one for the other.

Joyce O’Shaughnessy, MD: But that’s an important point.

Adam M. Brufsky, MD, PhD: That’s a big point, that’s huge.

Joyce O’Shaughnessy, MD: With the APHINITY trial, we’ve had an improvement in disease-free survival, particularly in the higher risk node-positive disease. So we’re backing away from that a little bit.

Adam M. Brufsky, MD, PhD: We’re probably going to.

Ruth O'Regan, MD: Then you have the MARIANNE trial showing an advantage.

Joyce O’Shaughnessy, MD: Yes, an advantage, that’s right.

Adam M. Brufsky, MD, PhD: So we’re going to extrapolate to that and say no pertuzumab, just T-DM1 in people who don’t have a PCR.

Aditya Bardia, MD, MPH: The way I’m seeing the results of KATHERINE are that it’s very similar to EMILIA. So if we look at the metastatic setting of first-line therapy with T-DM1, MARIANNE was a negative trial.

Adam M. Brufsky, MD, PhD: Correct.

Aditya Bardia, MD, MPH: EMILIA was positive, but that was second-line.

Adam M. Brufsky, MD, PhD: Correct.

Aditya Bardia, MD, MPH: And this poster has a dual setting and is kind of a second-line setting.

Adam M. Brufsky, MD, PhD: I agree with you; that’s the way I’m looking at it too.

Joyce O’Shaughnessy, MD: There was survival advantage with the EMILIA trial too.

Adam M. Brufsky, MD, PhD: That’s a great point. That’s a great way of looking at it.

Joyce O’Shaughnessy, MD: Right. And this has a big impact on survival. And also the TH3RESA trial, later line, was also a very positive trial on survival. So, yes, you really see the impact in that more resistant setting.

Heather L. McArthur, MD, MPH: What I’m really struggling with are the patients who are already on their adjuvant trastuzumab/pertuzumab, and maybe they’re 2 months in, 3 months in….

Adam M. Brufsky, MD, PhD: With residual disease.

Heather L. McArthur, MD, MPH: With residual disease, potentially, and what you’ll do. If they’re 6 months in, if they’re 9 months in, what are we going to do? Do you reset the clock?

Adam M. Brufsky, MD, PhD: That’s a great question, do you reset the clock?

Joyce O’Shaughnessy, MD: There are 14 treatments.

Heather L. McArthur, MD, MPH: With significant fatigue.

Adam M. Brufsky, MD, PhD: If you use it in the adjuvant setting, it’s not so benign. You don’t lose your hair, but….

Joyce O’Shaughnessy, MD: Yes, but you know what, these women can do it. They want the best outcome, basically.

Adam M. Brufsky, MD, PhD: But it depends.

Tiffany A. Traina, MD: Another potential impact of this T-DM1 is chemotherapy. So what happens with reconstruction along the way if it’s deferred? Do you need to defer it? I think ATEMPT allowed for reconstruction after a few months on T-DM1 if you were randomized to that arm.

Aditya Bardia, MD, MPH: Really? Oh wow.

Tiffany A. Traina, MD: I don’t know what happened in KATHERINE.

Adam M. Brufsky, MD, PhD: And in ATEMPT we don’t know what the rate of postoperative wound infection was, we have no idea yet.

Joyce O’Shaughnessy, MD: We have to see data. I believe that they are being collected so that’s very important, that’s great to hear. And I suppose that maybe has also happened in KATHERINE, that they may have been allowed. I don’t know that final count. But at least there are data on that. But that’s very interesting. I think it’s a discussion point, right? We go home, somebody’s been on 3, 4 months of their trastuzumab/pertuzumab. We go home and say, “Hey, we have these new data. It’s 11% absolute improvement.” Of course that depends on where you’re starting from.

Heather L. McArthur, MD, MPH: Again, for someone who’s 2 months into their adjuvant HER2 [human epidermal growth factor receptor2]-directed therapy, that’s an easier discussion than for someone who’s further along. “Surprise, you thought you were 1 month away from finishing and now I’m thinking about another agent.

Adam M. Brufsky, MD, PhD: They have patients who were N3. Did you see them in this trial? With someone who is N3, who’s been on it for a couple of months, I probably would think of fatigue. Maybe something like that.

Aditya Bardia, MD, MPH: A great point and it leads to the neratinib discussion as well. Say you go back to clinic on Monday, you have a patient who’s been on 11 months of trastuzumab who had significant residual disease. Would I do T-DM1, or would I consider neratinib for that patient?

Transcript edited for clarity.