DR GRADISHAR: We participated, back in the day, in the AC followed by TH trial. So we still view that as a very standard regimen. I don’t think there’s anything wrong with TCH, and maybe Dan will address this, but it comes to risk-benefit discussions of myelodysplasia, cardiac dysfunction, et cetera, et cetera, in trade-offs, but we still use AC → TH. With respect to the very low risks, we tend to think about a taxane alone, trying to avoid the anthracycline, and we’d be the first to admit we don’t know.
DR LOVE: Ian?
DR KROP: So for the patients who have higher risk disease, certainly lymph node-positive — any significant risk factor — we tend to use AC followed by TH, except in the patients in whom there are cardiac risk factors. Node-negative can still be relatively high risk if it’s a larger tumor or if it’s an ER-negative tumor. But for the real low-risk patients, for the 7-millimeter, ER-positive, node-negative cancer, even the 1.1-centimeter node-negative cancer, I think the problem is that we don’t have much data at all. Our institution has completed a study of 12 weeks of weekly paclitaxel with trastuzumab followed by 40 weeks of trastuzumab alone in 400 patients. But we don’t have the data for that yet.
DR LOVE: Chuck?
DR VOGEL: I have discussion between anthracycline and taxane-based therapy and TCH. We discuss the hazards of myelodysplasia, leukemia, congestive heart failure as part of that in-depth discussion. In general, I would say that I lean more towards giving docetaxel/carbo/trastuzumab, but after a fully informed discussion with the patient.
DR LOVE: Kathy?
DR MILLER: I probably still use more TCH than AC → TH, but that’s probably because the number of patients who truly have multiple positive nodes and really high-risk disease that I see is actually fairly small, and more of our patients are treated in the neoadjuvant setting. I think we’ve spent a whole lot of time arguing about something that we have very little data. So I spend most of my time trying to make sure that we identify all of the folks who are truly HER2-positive, who ought to get trastuzumab. If they get trastuzumab in some form, I’m relatively happy. And I think the rest is just more style than substance.
DR LOVE: Dan?
DR HAYES: In BCIRG 006, the original thought, which was a terrific hypothesis based on Dr Slamon’s very considerable preclinical data, was that there would be synergy between docetaxel, carboplatin and trastuzumab that one might not see with paclitaxel and trastuzumab. However, in every analysis that they have shown, the AC → TH arm Kaplan-Meier curves, for both disease-free and overall survival, is slightly better than the TCH arm. Not statistically so, but still enough that you can see space between the curves. Both of them always better than the ACT without H arm.What I just heard around the table is how most of us practice. Where your patient that you presented with many positive nodes who’s got a terrible prognosis and who’s young and healthy and no risk of heart failure, I think AC → TH is the right thing for her. Whereas a 70-year-old woman with some hypertension and maybe a little diabetes, who has a node-negative but 2- or 3-centimeter tumor, I think TCH is perfectly reasonable for that patient.