Chemoimmunotherapy in TNBC: The KEYNOTE-355 Trial

Transcript:

Joyce O’Shaughnessy, MD: In the metastatic area, there’s a trial that brings in a gemcitabine/carboplatin.

Heather L. McArthur, MD, MPH: KEYNOTE-355.

Joyce O’Shaughnessy, MD: KEYNOTE-355, that’s right.

Heather L. McArthur, MD, MPH: So, KEYNOTE-355 is the first line. You’re just testing me. So that’s looking at first line, very similar to the IMpassion130 population—metastatic triple-negative breast cancer, chemotherapy with or without pembrolizumab. And, yes, they have a gemcitabine/carboplatin arm, so that will answer a slightly different question.

Adam M. Brufsky, MD, PhD: But here’s my question about that trial: So, it’s physician choice; so, the choices are nanoparticle paclitaxel, paclitaxel, or gemcitabine/carboplatin.

Heather L. McArthur, MD, MPH: Right.

Adam M. Brufsky, MD, PhD: So, I don’t think we know yet how many are in each arm, right? They’re not equally distributed. It could be all paclitaxel for all we know, right?

Heather L. McArthur, MD, MPH: Correct.

Adam M. Brufsky, MD, PhD: So, how’s that going to help us? Because now we have nanoparticle pac. What’s the proper partner is where I’m going with this. We have nanoparticle paclitaxel, clearly with benefit. But now we have this trial, it’s unrandomized physician choice, whatever they decided to do. So, how are we going to fix that?

Joyce O’Shaughnessy, MD: Maybe the point estimates will be the same for all 3, do you know what I mean?

Adam M. Brufsky, MD, PhD: Let’s hope that when you do the forest plot, they’re all the same. And there are enough patients in each subgroup to be able to make that forest plot.

Joyce O’Shaughnessy, MD: Unlikely there will be huge differences, probably.

Adam M. Brufsky, MD, PhD: How big was KEYNOTE-355? Do you know the size?

Heather L. McArthur, MD, MPH: I think it’s 900.

Adam M. Brufsky, MD, PhD: So it is fairly substantial, all right. So, it’s a big enough trial.

Heather L. McArthur, MD, MPH: Around 900. But you’re right, it might be that we’ll be doing cross-trial comparisons because it’s mostly paclitaxel-, not nab-paclitaxel-, enriched population.

Adam M. Brufsky, MD, PhD: Or they won’t give a lot of the gemcitabine/carboplatin.

Heather L. McArthur, MD, MPH: They might not.

Tiffany A. Traina, MD: Is there also a difference in the time since recurrence—or disease-free interval, I should say—between IMpassion130 and KEYNOTE-355?

Heather L. McArthur, MD, MPH: There is, there is.

Tiffany A. Traina, MD: And so IMpassion130 is a year.

Heather L. McArthur, MD, MPH: IMpassion130 is a year.

Adam M. Brufsky, MD, PhD: And this is 6 months.

Heather L. McArthur, MD, MPH: And this is 6 months, exactly. It might be a more resistant population.

Adam M. Brufsky, MD, PhD: What’s going to happen to the other IMpassion trials? There’s IMpassion132, which is the less than 12 months recurrence, getting gemcitabine/carboplatin with or without atezolizumab, and then there’s the paclitaxel, the IMpassion131. What’s going to happen to those trials when KEYNOTE-355 announces? What are they going to do with those data?

Heather L. McArthur, MD, MPH: Well, as the co-PI [principal investigator] for the adjuvant atezolizumab chemotherapy study, I can tell you that this is an active area of investigation and discussions—a lot of discussion. I think generally—I don’t want to speak for the other investigators, but I think, generally speaking, the consensus is that we’re a little reluctant to make massive changes to existing studies based on 1 study. And given that so much data are imminent in the next few months, we have, at least for the time being, decided to hold the course but come up with plans B, C, and D in case we need to pivot in a timely fashion when those additional data come out.

Adam M. Brufsky, MD, PhD: Very good.

Joyce O’Shaughnessy, MD: Go ahead, Aditya.

Aditya Bardia, MD, MPH: I was just saying, in terms of the PD-1, I think the data were very interesting at the San Antonio Breast Cancer Symposium. Do we know much about the stability of PD-1 over time? And does archival versus fresh specimen matter? Have they looked at those subsets as far as PFS [progression-free survival] is concerned in IMpassion?

Heather L. McArthur, MD, MPH: It seems to be similar between the primary and the metastasis, where they evaluate the tissue. Whether it was earlier or later doesn’t seem to matter.

Joyce O’Shaughnessy, MD: So be sure to get a metastatic biopsy. That’s a difficult biopsy. You feel pretty comfortable you’re not going to shortchange the patient if you use the primary.

Heather L. McArthur, MD, MPH: Yes. Although that being said, again, 40% of the patients had de novo disease, and so is that tissue going to be more like primary tissue…? So I think there are still a lot more questions to answer.

Joyce O’Shaughnessy, MD: Yes, and for most patients, we’ll have both anyway. We could take a look.

Adam M. Brufsky, MD, PhD: And it’s only a 1% cutoff, too.

Joyce O’Shaughnessy, MD: One percent of immune cells.

Adam M. Brufsky, MD, PhD: It could be like 1% in the primary archival and 2% in the metastatic. It’s such a low bar to exceed.

Joyce O’Shaughnessy, MD: Yes, right, which is amazing. It didn’t make any difference if you were 1% or 1% to 5% or above 5%, you had the same benefit, is that right?

Tiffany A. Traina, MD: Yes, they just showed that.

Joyce O’Shaughnessy, MD: Yes, and they just showed that.

Heather L. McArthur, MD, MPH: That’s right. Leisha showed the Kaplan-Meier curves, which we hadn’t seen previously for PFS and OS [overall survival] for the PD-L1—negative populations, because we were wondering. We knew that there was improvement in the intention-to-treat population, but how much of that improvement was weighed by the PD-L1-positive? So she did show the PD-L1–negative PFS and overall survival curves, and those lines are dead on top of each other.

Joyce O’Shaughnessy, MD: So you’ve got to have it, but only 1%.

Heather L. McArthur, MD, MPH: One percent.

Transcript edited for clarity.