Adam M. Brufsky, MD, PhD: Now we’re going to change gears a little bit and talk a little bit about HER2-positive breast cancer. And I think, at this meeting, there was an update. I think there have been 2 fairly substantial trials presented in the last 4 to 5 months involving the therapy of HER2-positive early-stage breast cancer. One of them is the ExteNET study. And both Hope and Joyce were present at the United States ODAC FDA meeting for neratinib. And I’d like to at least start with Hope and ask her for her thoughts on the update that was presented at this year’s ESMO.
Hope S. Rugo, MD: ExteNET is a really interesting trial because of the way it has grown, shrunk, and grown over time. It is the original trial which thought if you get a year of trastuzumab as an adjuvant therapy with our chemotherapy, then you still have a risk of recurrence. So, maybe switching to a non—cross-resistant therapy would be effective in terms of reducing the risk of recurrence over time.
It’s fairly simple, and I think it’s a very rational approach. But as the TKI world changed and the antibody world changed for HER2-positive disease, there was a lot of moving around of the drug. So, the drug went from one company to another company to where it is now with Puma. And in the course of that, the ExteNET trial actually shrunk to be just under 3000 patients and have a 2-year endpoint.
So, we saw that 2-year endpoint. It was quite remarkably impressive, I think, in terms of showing a difference in disease-free survival and then also a difference that seemed to be more marked in the hormone receptor-positive population. Then they actually redid the whole way they were evaluating the study, so go out to 5 years and have a survival endpoint also. And patients were re-consented.
Here they presented the 5-year data, and actually 76% of the patients were re-consented, which was great. I think it was really good. The rest of the patients are centered at 2 years. And what’s nice to see actually—and it’s similar to what we’ve seen with the antibody data in HER2-positive disease—is that the data, as presented at 2 years, have been conserved. In other words, the curves continue to stay separate. There’s still a 2.5% difference in disease-free survival in the overall population and invasive disease-free survival. And then the difference between the hormone receptor-positive and hormone receptor-negative groups continue.
So, the absolute difference in hormone receptor-positive disease was 4.4%, but there wasn’t a difference in the hormone receptor-negative disease. Quite intriguing, I think, and shows that these data are here to stay and that there is efficacy. And, of course, that led to FDA approval, after the ODAC meeting, of neratinib as some post-adjuvant therapy, extended adjuvant therapy for HER2-positive breast cancer. Really thinking about the diarrhea and how to manage it for a drug like this has been really important. And it turns out that really everybody who takes neratinib should be taking prophylactic antidiarrheal therapy right up front—immediately, not waiting—because it’s an immediate effect that occurs early, and you can markedly reduce the amount of diarrhea by doing prophylaxis, which is great, and it goes away over time. So, also very good.
Adam M. Brufsky, MD, PhD: Michael, was there experience with the Gepar group in neratinib? I believe there was, was there not? You guys doing any trials?
Michael Untch, MD: We contributed, with some centers, to the study, but actually I was waiting to be asked about the APHINITY study.
Adam M. Brufsky, MD, PhD: Which we’ll get to that in a little bit.
Michael Untch, MD: I would like just to point out that the data are very convincing from the neratinib study, and it fits quite well with the GeparQuinto trial.
Transcript Edited for Clarity