Case 1: Treatment for Early-Stage HER2+ Breast Cancer

Hope Rugo, MD, FASCO: Adam, what do you recommend? What kind of neoadjuvant chemotherapy do you recommend for your patients who have HER2-positive breast cancer? Do you ever give less than AC-THP [doxorubicin and cyclophosphamide followed by paclitaxel, trastuzumab, and pertuzumab] or TCHP [docetaxel, carboplatin, trastuzumab, and pertuzumab]?

Adam Brufsky, MD, PhD: I usually give the full TCHP regimen to people who are T2 and above, and/or N1. They’ll get TCHP. I think that we have learned, though, from analogies to other smaller studies. At least in the metastatic setting, we probably could think about cutting the carboplatin if we really have to. I wouldn’t do that if I had a choice. As Ian said when describing his patient, I would definitely think about cutting the pertuzumab, if I have to, for a cycle or 2 because diarrhea does seem to be a bigger issue than I think a lot of us would have thought with this regimen, at least in my experience. In mine, it’s probably about 9%, 10%, 12%.

But generally, I try to do TCHP upfront and then, as we’re going to talk in a minute, what to do after they have had or are done with the therapy in terms of their response is a big debate. Not much of a debate, but I think that’s where the real concerns are right now.

Hope Rugo, MD, FASCO: It’s sort of a data-free zone, in many ways. Ian, do you also usually use TCHP as your backbone, or do you use a different approach? And is there a specific type of patient you might, for example, give THP [docetaxel, cyclophosphamide, and pertuzumab] and then make a decision?

Ian Krop, MD, PhD: I think that’s another area of real interest. We know that giving just THP is associated with a pretty significant pCR [pathologic complete response] rate, and there’s actually a large trial that’s just getting underway within the U.S. Cooperative Group that’s asking that specific question: Can you treat patients with moderate- to high-risk HER2-positive disease with just 4 cycles of THP? And then, if they have a pathologic complete response, can you not add any additional chemotherapy? It's a true de-escalation design. If they don’t have a pathologic response, then it is recommended they get additional chemotherapy in addition to the T-DM1 [trastuzumab emtansine].

My personal feeling is that outside of a clinical trial, right now the standard is just what Adam was saying. But I think there is a lot of interest in trying to cut back some of that chemotherapy, since we know that a substantial fraction of these patients are going to have very sensitive disease and will have a pathologic complete response with a taxane-based regimen alone.

Hope Rugo, MD, FASCO: Do you vary what you’re treating patients with based on their hormone receptor status?

Ian Krop, MD, PhD: I typically don’t, even though we know that affects the pathologic response rate. I’ve mainly based it on overall risk.

Transcript edited for clarity.