Standard of Care for Early-Stage TNBC

Joyce A. O'Shaughnessy, MD: Well, hello and welcome to this OncLive® Peer Exchange. I’m Joyce O’Shaughnessy from Baylor University Medical Center, Texas Oncology and US Oncology in Dallas, Texas. I’m really pleased to be joined here today for this virtual discussion with 4 of my colleagues, Dr Adam Brufsky from the University of Pittsburgh Medical Center; Dr Sara Hurvitz from the University of California, Los Angeles; Dr Kevin Kalinsky from Columbia University Medical Center in New York; and Dr Sara Tolaney from the Dana-Farber Cancer Institute in Boston.

Welcome, everybody. I’m so glad to be here with you today. Today we’re going to highlight a number of topics, mainly pertaining to triple negative breast cancer. First, we’re going to start by looking at some of the new data that came out from ESMO [the European Society for Medical Oncology Virtual Congress 2020] and putting that into the context of our day-to-day treatment of patients with earlier stage triple negative breast cancer. Then we’ll transition to the treatment of metastatic triple negative breast cancer, again focusing on the standard of care but also updating you on new data that came out from ESMO and putting that again in context. This ought to be a very interesting discussion because it’s always fun to look at the new data.

With that, let’s go ahead and get started. We’ll start with early stage triple negative breast cancer. Kevin, could you lead us off with a brief overview of some of the standards of care for early stage triple negative breast cancer?

Kevin M. Kalinsky, MD: Thank you, Joyce. I think that increasingly for our patients with early stage triple negative breast cancer, we treat with neoadjuvant chemotherapy. I think that this is for a number of reasons, so that we could see how patients are responding to the treatments that we’re giving. But importantly, if patients have residual disease, then based upon the CREATE-X data, we follow that with oral capecitabine. For patients with triple negative breast cancer, commonly these are anthracycline/taxane-based regimens. We did see some data at ESMO, the GeparOcto study, in which patients had different sequencing of chemotherapies, and this really didn’t ultimately change therapy.

In this particular study, patients received anthracycline/taxane followed by Cytoxin as opposed to weekly doxorubicin and paclitaxel. But ultimately for patients with triple negative breast cancer, based upon the chemotherapy-alone ESMO data, this didn’t really change practice. One of the questions I think that keeps coming up for patients is what should be the utilization of a platinum? I think that this is something that we commonly argue about, whether we should be adding, for instance, carboplatin to the neoadjuvant setting, and whether there are any biomarkers that can help inform which patients should be receiving that treatment, given that it has additional toxicity, including hematologic toxicity.

Joyce A. O'Shaughnessy, MD: Am I right that NCCN [the National Comprehensive Cancer Network] does not have preoperative carboplatin in its guidelines? Am I right about that? I know that historically, I want to make sure nothing had changed. It’s basically still ACT [doxorubicin, cyclophosphamide, paclitaxel], or for patients who can’t have an anthracycline, basically docetaxel, cyclophosphamide. But there are some platinum-based regimens, even docetaxel, carboplatin, from Priyanka Sharma, MD, and others. Kevin, when do you use platinum? Do you ever use platinum preoperatively?

Kevin M. Kalinsky, MD: I think the jury is still out. A part of this is that there hasn’t been consistent findings in terms of improvement of things, including overall survival rate differences that we saw from the German study compared to the Alliance trial. Even though there are differences in how the studies were designed and whether they were powered to actually look at that end point, I think that this is something that we’re still trying to define in the operable setting. I will think about utilizing that if I have a young patient with a large tumor, perhaps somebody who has a germline BRCA mutation.

I will also say that the data in the operable setting may not be as consistent as what we see in the metastatic setting. For instance, the TNT trial, the metastatic study for patients who have BRCA mutations, where we saw that giving a platinum may be better than giving a taxane. Going back to the operable setting, I think the jury is still out. Identifying which patients really benefit from a platinum still is an ongoing question.

Joyce A. O'Shaughnessy, MD: Thanks. For the most part, no, it sounds like, but the occasional high-risk younger or maybe germline BRCA patient. Let me get a couple of other viewpoints on that. Sara Hurvitz, how about you, do use platinum?

Sara A. Hurvitz, MD: I am compelled by Priyanka Sharma’s data. I try to avoid the use of anthracycline in a patient, for example, with node negative, triple negative breast cancer or 1 node positive. I want to use the neoadjuvant setting. I totally agree with Kevin in using the neoadjuvant setting to test the sensitivity of the tumor in vivoand see whether the treatment we’re deciding to use actually works. For the patients who have a robust response clinically and achieve a pathologic complete response with the taxane/platinum regimen, that’s a win-win because they’ve been spared the potential significant toxicities of an anthracycline.

However, on occasion we’ll have to change a patient to dose-dense chemotherapy with an anthracycline and/or give anthracycline on the back end if there is residual disease. It’s an area that is evolving. I think we have to follow the data and follow out the survival data, as Kevin mentioned.

Joyce A. O'Shaughnessy, MD: Neat. We’ve got the East Coast and then the West Coast with the avant-garde getting us away again from anthracyclines as they did, correctly so we might add, in the HER2-positive setting. How about you, Adam, do you incorporate platinum sometimes into the preoperative setting?

Adam M. Brufsky, MD, PhD: I personally don’t. There is a mixture in our practice, and I think that it reflects the whole uncertainty about the benefit of platinum and the toxicity of it. I think it is not a benign drug, especially if we give it weekly, or even every 3 weeks with weekly paclitaxel. You do get substantial thrombocytopenia, neuropathy, and neutropenia. That’s over and above the typical weekly paclitaxel we use, so it’s not a benign intervention. I agree with Sara that the data are quite mixed. If I’m going to give treatment to someone with node positive breast cancer, most of them will still get ACT.

I like the concept of going to TC [docetaxel/cyclophosphamide] and getting away from it, and eventually I will probably get there. I think node negative, I don’t usually do neoadjuvant therapy. They’ll all get TC times 4 anyway. Where I see the data is from the TNT trial, and I think a lot of what we see with the carboplatin may be explained either by BRCA or BRCA-like disease that we just haven’t really uncovered yet. That’s where I tend to still use platinum. I agree with the chemotherapy sensitivity thing that Kevin said, that while I’ll try somebody out on AC [doxorubicin/cyclophosphamide] or something like that, and if they don’t really respond and they’re younger and could tolerate it, I’ll add the carboplatin to the Taxol, that’s how I usually do it, or the paclitaxel. I think we’re all saying the same thing, that we try to figure out what that patient selection is for carboplatin. We just don’t know who it is that’s really going to…

Joyce A. O'Shaughnessy, MD: Now let me ask you, when you said you have a node negative patient who, let’s say, went to surgery first and she’s got node negative disease, T1C, you give 4 cycles of docetaxel and cyclophosphamide, or carboplatin?

Adam M. Brufsky, MD, PhD: Docetaxel/cyclophosphamide, as we know, looking back from a year ago, we have great data on several thousand patients. You look at the TAILORx chemotherapy data that anybody with a recurrent score, and this is ER positive, but I suspect this could be the same. You have a 90% to 93% event-free survival at 5 years. I’d love to see data in node negative triple negative disease that anything beyond TC times 4 is a benefit. I know we use a lot of ACT, and we use a lot of TC times 6, whatever. But where are the data that are driving that? The head-to-head randomized data that can tell us that this extra chemotherapy is really doing clinically…I’m sure there’s going to be some benefit, but is it clinically significant?

Joyce A. O'Shaughnessy, MD: Well, thank you. That’s why it’s not on NCCN guidelines, there’s just not a consensus that has come forward from the phase 3 trial data that we really need to have a uniform approach in clinical practice.

Transcript Edited for Clarity