Debu Tripathy, MD: Let’s move on now to the low-risk group of patients. We’ve started to split our treatment algorithms now…initially with the APT [adjuvant paclitaxel and trastuzumab] trial for the weekly trastuzumab for low-risk patients, which I think has been a great advance for our patients and now is being confirmed with longer follow-up. Joyce, do you want to talk about…the randomized trial that takes us to the next level of information?

Joyce A. O’Shaughnessy, MD: It was very interesting. The first data that came out for the ATEMPT trial were for patients with T1 and T0 for HER2-positive (+) breast cancer. There were 500 patients randomized 3 to 1 to T-DM1 [trastuzumab emtansine] for a year versus the weekly paclitaxel times 12 with trastuzumab followed by finishing the year of trastuzumab.… Sara M. Tolaney, MD, MPH, had published an update, I believe it was at 7 years, showing really spectacular results. There were low single digits and low numbers of distant recurrences, which is very good.

The results on both arms are very good. This was not really to be compared, it was more just a reference so there wouldn’t be bias for one arm versus the other. But the primary end point was clinically related toxicities: wanting to decrease it by at least 40% with the T-DM1, which wasn’t met. It was less with the T-DM1.

Ian E. Krop, MD, PhD: In the final analysis, this particular end point of clinically relevant toxicities was actually identical—46% in both arms. But I think one point to bring out is that the toxicity profiles of the drugs are different, as we all know. There was more, obviously more alopecia and neuropathy and neutropenia with TH [paclitaxel and trastuzumab], and there were more LFT [liver function test] abnormalities, thrombocytopenia and early discontinuation before the 1 year with the T-DM1 arm.

Joyce A. O’Shaughnessy, MD: Yeah, 17% like discontinued and the neuropathy…

Hope S. Rugo, MD: They all stopped in the last 6 months. Having put lots of patients in that trial— there was just a fatigue with getting it. It’s not trastuzumab. You have a bit more adverse effects, but they were doing fine up until then, which was fascinating. Actually, there was a study of PROs [patient-reported outcomes] where at the beginning… Everybody got randomized, and then they got their first PRO set of documents. The people who were randomized to T-DM1 did much better in terms of PROs before they’d been treated.

Adam M. Brufsky, MD, PhD: All because they know they’re not losing their hair.

Joyce A. O’Shaughnessy, MD: But neuropathy was less: 7% versus 2%—where 7% was TH and 2% was T-DM1.

Adam M. Brufsky, MD, PhD: But that’s still in the single digits. That’s not…

Hope S. Rugo, MD: Actually, what’s interesting is they looked at it at 18 months, and it’s 100 patients versus 300. That still makes me a little worried because there’s so much pharmacogenomics and individual sensitivity to taxanes in terms of neuropathy. But, given the fact that we don’t identify it, we have a subgroup of patients who really get long-term neuropathy from minimal exposure to taxanes—at 18 months there was less in the T-DM1 arm. So, it is a consideration for people. If we could do a shorter course—6 months—on somebody who’s a violinist, for example…you know? There are a lot of things where we can easily destroy somebody’s life by giving them more neuropathy.

Adam M. Brufsky, MD, PhD: The other question I have is I think 60% or 70% of the patients in ATEMPT were ER [estrogen receptor]-positive, triple-positive, correct? So how many of those patients were truly luminal A? In true dose escalation, how many patients need only hormonal therapy? That’s really the question.

Ian E. Krop, MD, PhD: We should be very clear that…the design of APT and ATEMPT doesn’t tell you.

Hope S. Rugo, MD: You need to treat.

Ian E. Krop, MD, PhD: This is for any of these, particularly for very small ER+ HER2+ cancers, you probably don’t need anything else besides hormonal therapy. But I think the take-home message here was that in patients treated with T-DM1, there were excellent outcomes.

Joyce A. O’Shaughnessy, MD: 97.5%, 3 year...

Ian E. Krop, MD, PhD: You can’t get much better than that. There were 2 occurrences out of 375 patients, but it was not dramatically better tolerated than TH. I think it’s hard to justify saying T-DM1 should be the new standard for stage I HER2+ breast cancers on the basis of these data. However, for patients in whom the toxicities of TH are a real issue—alopecia in some patients is a problem.

Hope S. Rugo, MD: And they can’t use scalp cooling.

Ian E. Krop, MD, PhD: Right. And neuropathy. There’s a lot of vocations that neuropathy, as you said, would be a real game changer. So, I think, for those patients, I think for T-DM1, these data say that for those patients, this is a potential option.

Transcript Edited for Clarity