Expanding Treatment Options for HER2+ Breast Cancer - Episode 4

TRAIN-2: Anthracyclines in HER2+ Breast Cancer

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Adam Brufsky, MD, PhD: Before we get into KATHERINE in the postneoadjuvant setting, let’s talk about one of the big adjuvant things that happened at ASCO [American Society of Clinical Oncology Annual Meeting] this year, and that’s TRAIN-2. Anyone want to take TRAIN-2? Who is the TRAIN-2 person today? Virginia, what do you think of TRAIN-2?

Virginia Kaklamani, MD: I don’t remember the last time I used an anthracycline for HER2 [human epidermal growth factor receptor 2]–positive disease. This is our way of using it in the metastatic setting when we have to, after we’ve given all the other agents. When you look at all the data, and you can talk about the BCIRG 006 study and how it was not powered to look at the 2 arms and the AC [doxorubicin, cyclophosphamide] arm was numerically superior and all that, but when you look at the neoadjuvant pertuzumab studies, it is pretty clear that the TCHP [docetaxel, trastuzumab, pertuzumab, carboplatin] arm has very good benefit. That’s why I’ve been doing that for a long time.

Adam Brufsky, MD, PhD: Does someone familiar with the design want to talk about that? Just so we can tell our viewers what it looked like? Carey?

Carey K. Anders, MD: TRAIN-2 was a randomized study that enrolled patients with HER2-positive breast cancer, stage II and III. One group got 3 cycles of FEC [fluorouracil, epirubicin, cyclophosphamide] followed by 6 cycles of TCHP. The other group got 9 cycles of TCHP, and then they completed HER2-directed therapy for the full year. About two-thirds of the patients were node positive, and path CR [pathologic complete response] was no different between the 2 groups, about 67% and 68%. There was no difference in the invasive disease-free survival or overall survival with the addition or subtraction of the anthracycline. They did report that febrile neutropenia was 10% in the anthracycline arm and 1% in the nonanthracycline arm. So pretty compelling data with path CR as well as longer-term outcomes.

The one question that comes to my mind is, would anybody start giving 9 cycles of TCHP? In my own practice, by the time we get to the sixth cycle of TCHP, most of my patients are pretty ready to move away from the chemotherapy portion. It answers a fantastic question, in terms of the anthracycline benefit, but it was a little different from how I traditionally give TCHP in my practice.

Mark D. Pegram, MD: In this trial it is very important to point out that the key was paclitaxel, not docetaxel.

Virginia Kaklamani, MD: That’s a good point.

Mark D. Pegram, MD: That’s why they get so many cycles. You’re right, nobody can tolerate 9 cycles of TCHP with docetaxel.

Adam Brufsky, MD, PhD: They were doing 9 cycles of the weekly T, paclitaxel, of THP [paclitaxel, trastuzumab, pertuzumab]. Is that correct?

Mark D. Pegram, MD: I think it was every 3 weeks.

Virginia Kaklamani, MD: I’d have to look back.

Adam Brufsky, MD, PhD: Let me talk to Rashmi at MD Anderson. You are like the dream of anthracyclines. How are you handling this?

Rashmi K. Murthy, MD, MBE: Since pertuzumab was approved back in 2012, the use of anthracyclines in the neoadjuvant setting for HER2-positive breast cancer has probably declined a bit. The time I use anthracyclines generally tends to be in the case of tumor heterogeneity. If we have a focus that was, for example, triple negative, plus the focus that was HER2-positive that we know about, then sometimes in that type of patient I might opt to use the AC followed by THP regimen. But most predominantly, I have been using TCHP, and I think the TRAIN data certainly support continued use of dual HER2 targeting, as opposed to use of anthracyclines.

Mark D. Pegram, MD: I stand corrected. It was weekly paclitaxel at 80 mg/m2 in TRAIN.

Adam Brufsky, MD, PhD: For how long? For what, for 9 months or 9 cycles?

Mark D. Pegram, MD: No, in 9 doses of the paclitaxel. The carboplatin was given 6 mg every 3 weeks.

Adam Brufsky, MD, PhD: That’s reasonable. Again, I guess the issue is we’re all settling on the fact that—a reasonable thing would be if you think there’s a lot of tumor heterogeneity, do the AC followed by THP. That is probably the last place I would go with it, but short of that anthracyclines and this disease may be forever on the way out. Remember the topoisomerase II amplification 10 years ago, Mark? We used to go around: That is anthracycline; you’re topoisomerase II amplified. How far we’ve come.

Transcript Edited for Clarity