Transcript:Adam M. Brufsky, MD: Hello, and thank you for joining us for this OncLive TV Peer Exchange. Today, we’re going to be talking about advanced breast cancer. Better understanding of breast cancer biology has led to important advances in terms of developing novel targeted and immune therapies. However, metastatic breast cancer remains an incurable disease for most women. As novel agents for treating advanced breast cancer continue to evolve, we need to continue to learn how to best use them, how to optimally sequence them, and how to safely combine them.

In today’s Peer Exchange, I am joined by several well-known experts in the field of breast cancer research. We’ll discuss the most recent studies in advanced breast cancer, including those presented at San Antonio in 2015, and provide important context to help you understand how the new data fit into your current treatment approach.

I am Adam Brufsky, and I am a professor of medicine at the University of Pittsburgh and the medical director for the Women’s Cancer Center at Magee Women’s Hospital at University of Pittsburgh Medical Center and the University of Pittsburgh Cancer Institute.

Joining me today are Dr. Sara Hurvitz, associate professor of medicine, director of the Breast Cancer Clinical Research Program, and associate professor of medicine in the Hematology/Oncology Division at the David Geffen School of Medicine at UCLA; Dr. Joyce O’Shaughnessy, chair of breast cancer research at the Baylor Charles A. Sammons Cancer Center, Texas Oncology, and US Oncology in Dallas; Dr. Hope Rugo, professor of medicine and director of breast oncology and clinical trials education at the Helen Diller Family Comprehensive Cancer Center at the University of California in San Francisco; and finally, last, but definitely not least, Dr. Christy Russell, associate professor of medicine at the University of Southern California in Los Angeles

Thank you to each of you for joining us today, and now let’s get started.

The management of advanced hormone receptor—positive disease has evolved with data from several prospective studies helping refine the way we use endocrine therapies, including combining them with targeted drugs. Let’s first review some of the data surrounding some of these hormone-driven breast cancers. And Christy, let’s start talking.

Before we start talking about advanced disease, I think that, at least in San Antonio, there were a few very interesting kinds of abstracts which really are part of a theme playing kind of for early stage disease in a way. And I think the real question now that we’re asking ourselves is, who really needs to be treated with chemotherapy? What types of patients need to be treated? Can you comment on that a little bit?

Christy A. Russell, MD: Absolutely. So if we go back to 2001, where the National Cancer Institute came out with guidelines suggesting that all women with tumors at least over 1 cm that we are positive should be offered chemotherapy. That’s the basis for these predictive and prognostic genomic tests being done to try to understand who may not benefit from chemotherapy.

So, there are multiple genomic studies and groups that have arisen, and probably the ones that have the greatest amount of data at this point are those created by Genomic Health and the OncotypeDx Score. So the test has been validated in women with ER-positive, HER2-negative, lymph node-negative breast cancer. And I think we all assume and have standardized that for the majority of our patients who meet the criteria for the original trials.

But the concern always has been for the patients who fall into this intermediate group, which Genomic Health has defined as an 18 to 31 recurrent score: are there patients in there who do benefit from chemotherapy? Presumably, those who are in the higher level are the ones who are having a majority of benefit, and the ones who are below 18 seem to get no benefit from chemotherapy.

So TAILORx was created, not by Genomic Health, but by ECOG and the Intergroup to run a study looking at can we better define those patients in the intermediate group who may or may not benefit from chemotherapy. And so as part of that, the group redefined what they viewed as the intermediate group that they wanted to test the theory of endocrine therapy with or without chemotherapy. And rather than using the 18 to 31 that was the original data from Genomic Health, they brought the numbers down and called the intermediate group 11 to 25.

And Joe Sparano, who’s talked about this a lot—and he’s the one who’s now presented the data on the low-risk group from TAILORx—has said the reason why that was done was because they didn’t want to have women who were undertreated. And the concern was that if they ran up to 31, it would put some women at a disadvantage of not being offered chemotherapy.

Adam M. Brufsky, MD: Do you really believe that?

Christy A. Russell, MD: No.

Adam M. Brufsky, MD: That’s a really good question. I mean, on paper, Joe has taken a lot of grief from a lot of us. I think that my understanding of it was that it was the lower end of the 95% confidence interval.

Hope S. Rugo, MD: That’s what mine is too.

Adam M. Brufsky, MD: Right. Is that kind of what it was? But Joe says it’s more for undertreatment now. Is that kind of what he’s saying?

Christy A. Russell, MD: Well, that’s what all the verbiage is.

Adam M. Brufsky, MD: Right.

Christy A. Russell, MD: But they created the 11 to 25. They said, ‘Let’s go to the higher end of the confidence intervals.’ And so they used that the 10% distant recurrence risk would fall at 11—not the median but the higher level of the confidence intervals—and 25 was the higher end, for 20% risk of metastatic recurrence.

Hope S. Rugo, MD: You can’t really knock it because whatever they did was really successful. They accrued patients to a randomized trial in the US in record time, and they got a huge number of people.

Adam M. Brufsky, MD: How fast was that accrual? It was pretty quick. It was like 3 1/2 years or something.

Christy A. Russell, MD: Yes, it’s very, very fast.

Adam M. Brufsky, MD: It was very, very quick. Okay.

Christy A. Russell, MD: So, what has now been reported: of the 10,000 women who went into this trial, there are 6800 who are in that intermediate group, all of whom are being given endocrine therapy and randomized to what are today’s standard chemotherapy versus not. And the women who were over 25 were obligated to endocrine therapy plus chemotherapy. And the women who were 11 or under are obligated to endocrine therapy alone and not chemotherapy.

So the first group, through that, they’re presenting are the women who are 11 and under who just received endocrine therapy, and they have a median follow-up now of about five years for that group of women. And what it showed was that the risk of distant metastases from this primary cancer within five years is 1%. And so there’s no way you’re ever going to be able to see a benefit from chemotherapy for that group obviously, and it’s really extraordinary to see how well that group of women is doing.

And so when they looked at other parameters of disease-free survival and recurrence-free survival, really the majority of events are not related to recurrence of metastatic breast cancer but secondary cancers, contralateral breast cancers, deaths from other causes. So it’s wonderful to see this group of women doing extraordinarily well in that group of 11 to 0 down. But I think there are the people we’ve already taken for granted that we would never give them chemotherapy.

Hope S. Rugo, MD: I think it’s kind of interesting because the group, the size of the tumors, was really small. And, of course, the question we all would have liked to have answered was, what if it’s 5-cm tumor? In the next set of studies, what happens in a node-positive patient where you know their risk of recurrence is very high? So are you impacting it with chemotherapy or are you not? You know they already have a bad prognosis.

Adam M. Brufsky, MD: Well, and so that brings stuff that was comparative. TAILORx got published in the New England Journal of Medicine, right? You know, a couple of months ago showing another 11 to less group. They’d had no benefits of chemo. They’re just so low risk it didn’t matter.

Hope S. Rugo, MD: Correct. They had a great outcome.

Adam M. Brufsky, MD: Great outcome. And so the issue is, but what does that tell us, as Hope just said, about those bigger tumors, about women who are node-positive; about the women, God forbid, who are HER2-, ER-positive, or triple-positive. I mean what is that going to do?

Transcript Edited for Clarity