Latest on Immunotherapy in Triple-Negative Breast Cancer

At the virtual San Antonio Breast Cancer Symposium (SABCS), researchers presented findings from two clinical trials -- KEYNOTE 522 and KEYNOTE 355 -- showing that the immunotherapy pembrolizumab (Keytruda), in combination with chemotherapy, delayed triple-negative breast cancer growth or spread.

MedPage Today has brought together three expert leaders in their field -- moderator Virginia G. Kaklamani, MD, of UT Health San Antonio, Ruth M. O'Regan, MD, of the University of Rochester Medical Center in New York, and William J. Gradishar, MD, of Northwestern University Feinberg School of Medicine in Chicago -- for a virtual roundtable discussion on these findings and other practice-changing data from the meeting. This is the first of four exclusive episodes.

Following is a transcript of their remarks:

Kaklamani: Hello. My name is Virginia Kaklamani, professor of medicine at UT Health San Antonio, MD Anderson Cancer Center, and leader of the breast cancer program. Today I have with me two esteemed colleagues: Dr. Ruth O'Regan, who is chair of medicine at the University of Rochester; and Dr. William Gradishar, who is the chief of division of medical oncology at the Northwestern University. We're going to be talking about the San Antonio Breast Cancer Symposium 2021 highlights and themes.

Our first topic today is going to cover immunotherapy options. And what I wanted to discuss -- Dr. Gradishar, I'll start with you -- is two of the KEYNOTE studies, both called KEYNOTE: KEYNOTE 522 and KEYNOTE 355, and the updates from SABCS. What are your thoughts on those trials?

Gradishar: Immunotherapy has found a foothold in the treatment of breast cancer, and I think it continues to evolve. So the two trials you're referring to, one in the metastatic setting and the other in the neoadjuvant adjuvant setting, have changed how we approach patients with triple-negative breast cancer. So it's interesting at the outset, that certainly in the metastatic disease setting we require knowing the PD-L1 status. And in the KEYNOTE [355] study, they did require that you have a CPS [combined positive score] score done. And what the data from this update shows us is that if you look at it more granularly, that in patients clearly who had a CPS score greater than 10, there was a clear benefit from the addition of pembrolizumab. And they further broke it down into those patients with the score above 20 and in those patients with the score less than 10.

And for those with [CPS] above 20, there was even somewhat numerically a greater benefit from the addition of pembrolizumab. So certainly anybody with a score above 10 would be a candidate to receive pembrolizumab and expect that there would be some potential for benefit. Whereas those with the score less than 10, there's really no observed benefit from the addition of pembrolizumab.

So I think that we have a bit more of a granular insight into who the patients are that are going to benefit. We also know from the updated data that there doesn't appear to be any toxicities that we need to worry about that weren't previously reported. So again, I think it's reaffirming, if anything. And then in the neoadjuvant study, the trial that looked -- KEYNOTE 522 -- that looked at the use of pre-op chemo alone, or pre-op chemo with pembro to be followed by pembro or not in the adjuvant setting. We again see the same improvement in outcome for the patients who got pembro. And importantly, here we don't need to know the PD-L1 status. It's not a critical element to making the decision, but rather that patients have triple-negative breast cancer. So the event free survival looked good. It appeared to be an effect that was seen across subsets of patients.

So I think what this really tells us is that if you have a patient who would've met the criteria for the KEYNOTE study in the pre-op setting, then this would be an appropriate patient to consider for the addition of pembrolizumab.

Kaklamani: So some of the questions that arise really have to do with pathologic complete response [pCR] versus not, and whether we should continue pembrolizumab in the adjuvant setting, whether we should add capecitabine. What are your thoughts in the different situations? Let's say somebody has achieved a pCR with the pre-op KEYNOTE 522 regimen. Would you continue pembrolizumab or would you stop it?

Gradishar: Well, I think it's a good question, not answered by the trial, of course. But I think one way of making that determination in the absence of good data, at least in my mind, is if the patient had significant toxicity or something from the addition of pembro and got a pCR, I would probably be tempted not to continue pembro in that setting. Keep in mind that, again we don't know the answer to that question based on the design of this trial. We also know if you look at the toxicity data, even though I was using that as an example how I might make a decision, most of the toxicity was seen upfront when you were giving concurrent chemotherapy and immunotherapy, as opposed to the post-op setting where the frequency of significant toxicity was much less because the chemotherapy's not there anymore. But in the patients who had a pCR, right now I'd probably continue the pembro unless there were some circumstances not to. And if the patient had a pCR, I don't know that I would add capecitabine in that setting, but certainly if they did not I would be tempted to do so. But again, the KEYNOTE study did not allow patients to have a pembro plus capecitabine as part of their treatment plan.

Kaklamani: So Dr. O'Regan, if you have a BRCA-positive patient, they're on the 522 trial, they're triple negative, they do not have a pCR and they would've been eligible for the OLYMPIA trial, would you continue pembro and add olaparib [Lynparza], but would you just give olaparib to that patient?

O'Regan: Yeah, I think that's a great question. I probably would continue the pembrolizumab and add the olaparib because we do have data from the metastatic saying showing that you can give them safely together. And likewise, I actually had a patient this week who had received pembrolizumab pre-op didn't have a pCR, and is not a BRCA mutation carrier, and I'm going to give her capecitabine and continue the pembrolizumab. So I think that as long as there's safety data, I think it's reasonable to do this.

Kaklamani: Thank you.

Gradishar: And I would agree with that example. I think that we have some safety data from other settings where cape and pembro can be given, of course. And I would try to maximize the potential benefit in somebody that didn't get a pCR.

Kaklamani: Thank you both.

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