Joyce A. O’Shaughnessy, MD: Aditya, let’s turn a little bit to the metastatic triple-negative setting. Say a few words, if you would, about some of your general approaches to chemotherapy in the metastatic setting—so outside of clinical trials. And what do you think about the data that Hope Rugo updated us about at San Antonio, with the nab-paclitaxel/bevacizumab versus the paclitaxel/bevacizumab in the triple-negative subset?

Aditya Bardia, MD, MPH: If I’m seeing a patient with metastatic triple-negative breast cancer, I think the first branch point is whether it’s de novo metastatic disease, was it someone who has disease recurrence after prior adjuvant or neoadjuvant therapy? If someone has de novo metastatic disease, the choices are essentially taxanes versus platinum, and we can use the DNT trial data to guide whether we should use a taxane versus platinum. And as a reminder, the DNT trial showed that there was no real difference between the use of a platinum versus a taxane, except for the germline BRCA group. So, unless someone has a germline BRCA-positive tumor, I would probably start with a taxane. Taxanes do work in breast cancer, including triple-negative breast cancer, and are better tolerated.

So, I tend to use a taxane first. And then upon disease progression, we have various options one could consider. You could consider a platinum, you could consider eribulin, or you could consider an anthracycline. So, these are all of the options that I would essentially sequence when seeing patients with metastatic disease.

On the other hand, if I have a patient who has disease recurrence, within a short period of their adjuvant chemotherapy or the neoadjuvant chemotherapy—during which that patient has usually seen an anthracycline plus a taxane—then I would be more inclined to use platinum as a first-line agent. Then upon disease progression on platinum, consider eribulin or some of the other chemotherapy agents. But I would also emphasize that for metastatic triple-negative disease, and actually for breast cancer in general, I tend to think of clinical trials. And if there is a clinical trial of a platinum agent plus something else, or one of these novel ADCs or targeted therapies, I would tend to consider that as well.

Joyce A. O’Shaughnessy, MD: Yes.

Aditya Bardia, MD, MPH: Now, as far as the differences between the various agents, I think paclitaxel versus Abraxane, in the data that Hope presented, essentially show that paclitaxel is a good agent. The Abraxane is similar to paclitaxel. Maybe slightly inferior in the metastatic setting—it tends to be associated with more adverse events—but that’s splitting hairs. And if I have a patient who has diabetes or there’s concern of hypersensitivity to taxane, I would feel very comfortable using Abraxane. And also consider using Abraxane with immunotherapy, because you don’t have to worry about the use of steroids. The ongoing trials that are using PD-1 inhibitors in the metastatic setting are using Abraxane as a backbone. So, that is something that I would consider.

Joyce A. O’Shaughnessy, MD: How about you guys? What do you do metastatic-wise, from the chemotherapy approach but also the nab-paclitaxel and the paclitaxel question?

Tiffany Traina, MD: I think I would echo a lot of what Aditya had said. And for our patients with TNBC, they may have very well received 5 agents in the early-stage setting between an anthracycline, a taxane, a platinum, or capecitabine. So, a patient with first-line metastatic triple-negative breast cancer is not the same as first-line ER-positive metastatic breast cancer. They’re already potentially heavily pretreated. And I think it’s critical to mention, as you really started this afternoon with, getting tissue at that time of metastatic disease at diagnosis and really the tumor genomic profiling on that material. Because after exposure to all of those drugs, we’d like to see what is there—confirm we’re still talking about triple-negative breast cancer; hopefully have a mutation that’s potentially targetable. So, I think a clinical trial in the first-line setting is very appropriate for these patients. I do find that I move eribulin up sooner than perhaps in the EMBRACE trial that was previously published. But I really start to look for nonchemotherapy options. And one of my early branch points is, what is the germline BRCA status and what is the androgen receptor status? And then, start to divide the heterogeneity of TNBC into buckets right at that first-line setting.

Joyce A. O’Shaughnessy, MD: Yes, real nice. How about you, Claudine?

Claudine Isaacs, MD: I would echo what has been said. Obviously, we’re looking at immunotherapy as well, and we’ll get to that in a few moments. Just to go back to Hope’s presentation from the CALGB trial, you know, overall, we remember that trial. It was trying to look at ixabepilone versus nab-paclitaxel versus paclitaxel. And overall, the take-home message from that trial was that the paclitaxel was better. What she presented was interesting, and again, these were exploratory analyses, so we need to be careful. But it looked like if you looked in the triple-negative subset, the nab-paclitaxel might be a bit better. Whereas in the ER-positive, it was paclitaxel that was better. So, I think what it does is it tells us that that is an active drug in that patient setting. And the dose as well in that CALGB trial is not a dose that we typically use. So, I don’t think the toxicity data reflect what is the more common use of the nab-paclitaxel. But again, those were subset analyses. Another interesting point to just tuck away there.

Joyce A. O’Shaughnessy, MD: Yes, that’s right. It’s a tuck-away point, and it reminds me of the tnAcity data a little bit, which Denise Yardley just recently published. It was a frontline triple-negative metastatic setting. In other words, you have to pick a doublet because somebody’s really got visceral crisis or is very, very ill. Which doublet do you go to? Is it gemcitabine/carboplatin? Is it nab-paclitaxel/carboplatin? Or is it nab-paclitaxel/gemcitabine? Paclitaxel/carboplatin was not in that trial, but the clear winner, on the PFS, was clearly the nab-paclitaxel/carboplatin at about 7.4 months versus about 5 months, where the other was a stat sig no difference in survival. You know, well tolerated certainly in a day 1-day 8 regimen, quite well tolerated. Again, no comparison to the paclitaxel there, so we really don’t know. But that particular doublet was the winner. And it’s just interesting, the nab-paclitaxel coming up in the metastatic setting in the triple-negative patient group is potentially better than paclitaxel.

We’ve seen similar data in the preoperative setting, too, from GeparSixto, where the path CR rate was higher with the nab-paclitaxel over paclitaxel in the triple-negative setting. It’s a head scratcher, isn’t it? But this is interesting. It’s like one of those tuck-away deals. And the only other point that I would make is that from the kind of triaging we do in the beginning, I just try not to miss what I call the Isakoff patient, the person who I could potentially cure; first-line metastatic, triple-negative, that 11%. I use the cisplatin because cisplatin had doubled the long-term durable CRs and the carboplatin is in that parenchymal lung lymph node breast group. It was not your bone livers. Your bone livers were not in that winner’s circle, if you will. It was parenchymal lung, not pleural effusion; lymph node; or in breast disease. There’s a small percentage that gets the cures. So, I try not to miss those patients there.

Transcript Edited for Clarity