Metastatic Triple-Negative Breast Cancer

Transcript:Adam M. Brufsky, MD, PhD: We’re going to switch over. I think we really have 2 subtypes of breast cancer—ER-positive and HER2-negative or HER2-positive—that have a lot of really good and exciting data. We’re getting now into triple-negative disease, where we have fewer things, although I think that there are the beginnings of the notes for excitement. Denise, how would your approach be now for someone who walks in the door with metastatic triple-negative disease?

Denise A. Yardley, MD: I think the backbone still remains chemotherapy currently. I think the first thing we do is look at clinical trials. I think this is a group where there was the most enthusiasm of singling them out for clinical trials, and there’s an abundance of trials with lots of different targets. They’re all still signal finding, but I think the signals that have emerged have been exciting. I think what we’ve also learned is that triple-negative isn’t a one-size-fits-all disease, so there’s a lot of heterogeneity that is encompassed by the term “triple negative.”

Within that are subgroups of patients, and we’re learning to try to find out a way to identify them that’s going to be reliable, reproducible. So, you have the group that’s the most sensitive to androgen receptor therapy, the LAR group, in the triple-negative setting. For those patients, their biology, their disease course, is very different, and so the strategies are really looking at some of the androgen receptor inhibitor agents that we may talk about. For immune therapy, I think there are lots of interesting signals. There’s a group that does seem to respond and have durability with just immune therapy, and I think there’s a lot of enthusiasm in combining our standard chemotherapy agents with immune therapy. And so, I think the first thing to do is look at our clinical trial menus.

And then, I still embrace chemotherapy for these patients. There are lots of signals—maybe there are advantages to platinums in these patients in the metastatic first-line setting. Most of them haven’t gotten a platinum in the adjuvant setting, although that’s changing now a little bit, too, so we consider that. I think the iniparib data put gemcitabine/carboplatin as a combination. Some of these patients have large tumor burdens, maybe more symptomatic relapses in a short amount of time from their taxane exposure, so doublets have been utilized in that first-line setting. I look at a lot of agents and try to tailor them to the patient—what we can glean from their history, how long that disease-free interval has been since adjuvant therapy.

Adam M. Brufsky, MD, PhD: I want to just interject one thing. Yesterday, CREATE-X was published in the New England Journal of Medicine. We were all waiting for this. Just for our audience, these are women with all stages and all subtypes of breast cancer, a Korean and Japanese population. It was a very large trial—900 women were randomized to no therapy or adjuvant capecitabine afterwards. And in the triple-negative subgroup of patients, the 5-year disease-free survival in the New England Journal of Medicine paper had a difference of about 10%. It was about 69% versus 56%.

Carlos L. Arteaga, MD: After how long of a follow-up?

Adam M. Brufsky, MD, PhD: About 3 to 5 years. It was a fairly substantial follow-up. So, the issue is that this didn’t make any sense with all the neoadjuvant studies that have been done, but is capecitabine now a favored drug for triple-negative breast cancer? Will we start using it in triple-negative breast cancer more often?

Debu Tripathy, MD: Remember, this is the only trial that focused on those who had residual disease. The other capecitabine and anti-metabolite trials were borderline positive, some of them, but they gave treatment to everyone. So, the question here is that you’re taking in an exceptionally high-risk group of patients. The study was positive overall in the whole group, both hormone receptor-positive and hormone receptor-negative, but if you broke it down, clearly the benefit was mostly in the hormone receptor-negative patients. I think it’s real.

There are a lot of questions as to whether or not that population may metabolize fluoropyrimidines differently. We know that they do. In fact, there are more fluoropyrimidines approved in Japan and Korea than there are in the United States for that reason. So, maybe some can argue that it may require a confirmatory trial in a more diverse population, but, nevertheless, I think it’s a positive study. It was designed that way and for that group of patients. I think it’s reasonable. In fact, the NCI has been asking the Cooperative Groups who have that study design, post-neoadjuvant trial, to change. They have the ECOG study.

Adam M. Brufsky, MD, PhD: Now capecitabine versus platinum.

Debu Tripathy, MD: And then there’s an immunotherapy study for residual triple-negative disease…

Adam M. Brufsky, MD, PhD: Right, with pembrolizumab.

Debu Tripathy, MD: Where they are now allowing postoperative chemotherapy.

Adam M. Brufsky, MD, PhD: But I guess the question is—bringing us back to triple-negative for a minute—does this now mean this is a go-to drug for us in triple-negative disease? Are you going to extrapolate those data in the triple-negative setting?

Debu Tripathy, MD: In that situation?

Adam M. Brufsky, MD, PhD: In that setting. But in the metastatic setting, will you extrapolate it?

José Baselga, MD, PhD: No, because the cause could be biology. I think that we know for triple-negative disease that recurrence occurs immediately very, very early on. It could well be that in this trial, what you’re treating is actually subclinical disease that is about to recur. So, I think it’s as much biology as mechanism of action.

Transcript Edited for Clarity