Advanced Breast Cancer: Expert Perspectives On Recent Progress - Episode 4

KEYNOTE-355 Regimen’s Role in Treatment Paradigm

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Joyce O’Shaughnessy, MD: One other point I want to bring out about the KEYNOTE-355 trial was that when you look at the forest plot, and I think, Hope, you alluded to this, the 2 taxane options, the nab-paclitaxel and the paclitaxel, the hazard ratio with the addition of the pembrolizumab was in the 0.5 ballpark. It was quite robust with regard to PFS , very impressive. The point estimate with gemcitabine and carboplatin with the addition of pembrolizumab was not as striking, it was 0.7, 0.74, or something like that.

It is because the patients who recurred quickly were allowed on the trial. As Hope described, as long as they had made 6 months, they were still allowed, and that's a very poor prognosis subgroup. By protocol, they were required to get the gemcitabine, carboplatin. The gemcitabine, carboplatin were the patients who had the poorest prognosis. I think that the choice of gemcitabine, carboplatin and pembrolizumab would be a very reasonable choice. In other words, I'm not deterred at all by those data, and I want to hear from you guys.

Hope, how are you going to decide? Let's say pembrolizumab is fully approved; we don't have OS yet, but where might you think about using gemcitabine, carboplatin, plus pembrolizumab, for example?

Hope S. Rugo, MD, FASCO: To comment on the approval, I do think it is likely that we'll need an overall survival, but of course we don’t know. I hope that we’ll see that in the not too distant future. But I think that we would use the same criteria that I used when I enrolled patients on KEYNOTE-355. It's patients who did not respond to neoadjuvant taxanes and progressed at 6 months or greater; I would choose gemcitabine, carboplatin. We do have a difficult situation in those patients.

I think we're interested to see if we can capture more of those patients by treating them in the neoadjuvant setting, for example, or post-neoadjuvant setting. I doubt it because if you think about it, if you had residual disease, I don't think post-neoadjuvant treatment will work because you're going to give them capecitabine for 6 months. By then, those people will have started to recur, so you're not going to capture them by giving them a checkpoint inhibitor after that.

That's where our differentials are in clinical practice when we don't use checkpoint inhibitors, and I would use the same. I tend to use nab-paclitaxel if a patient has already seen paclitaxel in that setting at 100 mg per meter squared. Certainly that's the dose we used in IMpassion130. There are some data in the neoadjuvant setting and others that suggest that higher doses are more effective, but it's never been definitive, and you get so much neuropathy, you're limited on duration.

Joyce O’Shaughnessy, MD: Thank you. Denise or Tiffany, any other comments about the gemcitabine, carboplatin in KEYNOTE-355?

Tiffany A. Traina, MD: I would echo what Hope has said, and I think that our neoadjuvant and adjuvant approaches are rapidly changing with emerging data about the use of checkpoint inhibitors. Interestingly, we have the I-SPY data of pembrolizumab in the preoperative setting. We have neoadjuvant data there suggesting benefit. It'll be interesting to see what happens if that is really moving into the earlier space, how we're treating our patients who recur, whether it's 6 months or later in that first-line setting, who remain PD-L1 positive.

Joyce O’Shaughnessy, MD: Exactly. How about you Denise, any final thoughts on KEYNOTE-355?

Denise Yardley, MD: I echo the practice comments that both Hope and Tiffany have made. It's a nice ability to welcome and embrace another chemotherapy combination with immunotherapy in triple negative breast cancer. I think a lot of those patients have been taxane-exposed and have toxicities, and there are limitations in being able to deliver that. Being able to have gemcitabine, carboplatin and feeling good about that combination and the results of those combinations, although we're still waiting on the survival, will be a welcome addition. Because there are many patients who either have toxicities with the taxanes or aren't good candidates, from neuropathy, from other medical conditions like diabetes, that now gives us a way to continue to deliver what we think is going to be our standard of care with immunotherapy in that population.

Joyce O’Shaughnessy, MD: Right, well said. More options to decrease toxicity and increase efficacy for patients. Real nice data.

Transcript Edited for Clarity