Mohammad Jahanzeb, MD: When we talk about HER2 blockade in the adjuvant setting, the first most exciting thing to point out, that it is perhaps the most major advance we have made in the treatment of breast cancer in the past few decades, is that we have been able to cut the risk of death by one-third to one-half, and that’s very exciting. A corollary of that is we are seeing fewer and fewer relapses. So, the fraction of patients who are de novo metastatic with HER2-positive disease has really grown because of reciprocal shrinkage of the other group, which is relapsed disease. It’s difficult to find these patients for clinical trials now, and that bodes well for our patients.

Where the field has headed, obviously, is better patient selection, knowing the mechanisms of resistance ahead of time so that we don’t give ineffective therapies to patients where it will not work and try to increase the efficacy further. In patients with smaller tumors, we are to de-escalate the therapies. Just like I said, we don’t give them combination chemotherapy; we give them just 12 weekly doses of paclitaxel, but that still causes alopecia. So, now there’s another trial that has completed accrual called ATEMPT, where patients receive T-DM1, or trastuzumab emtansine, compared with this approach of 12 weekly doses of paclitaxel and completion of 12 months of trastuzumab, hoping that we will de-escalate the toxicities and avoid alopecia. Even though we cannot further improve on the efficacy, which is already at 98%, you can’t really go much above 98%; there’s not much upward room.

Transcript Edited for Clarity