VIDEO: Optimizing treatment approach after chemotherapy in triple-negative breast cancer

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I think one of the most exciting things about triple negative breast cancer, and now I'm talking about early stage triple negative breast cancer in the past few years, is the KEYNOTE-522 regimen has really been associated with a much higher rate of pathologic complete response than we had previously seen. And there has also been the highly significant benefit associated with the addition of pembrolizumab to standard chemotherapy. Everyone knows, I'm sure, the KEYNOTE-522 regimen was associated with the pathologic complete response rate of around 65% for triple negative breast cancers who met the criteria. And because of that high success rate, there have been several questions that have been asked. And one of them is if someone does end up having a pathologic complete response afterwards, we do know that their survival is excellent. There was a recent analysis published in the Annals of Oncology, which looked at the additional benefit of pembrolizumab for people by residual cancer burden. So whether they were RCB-0, RCB-I, RCB-II, RCB-III, et cetera. And what they found was that there was benefit regardless of what the residual cancer burden status was. However, what was very, very encouraging is the event-free survival and the event rate was extremely low in people with the RCB-0. So for instance, at 39 months of follow up for people with RCB-0 who received pembrolizumab, the event rate was only 5.2%. Most of those were distant recurrences, but still that is a very low recurrence rate. And it's okay that follow up was shorter, because as you know, most triple negative breast cancers if there are gonna recur, will recur within the first five years. And so this has led to a clinical trial now, which is currently enrolling, which is called the Optimized PCR Trial. And what that trial asks the question of is maybe you don't need to get pembrolizumab after you finish neoadjuvant chemotherapy of a residual cancer burden of zero. So people will be randomized to either observation or adjuvant pembrolizumab. And I think this is a very important question to ask because number one, if you don't need the adjuvant pembrolizumab, then you really would like to drop it to avoid the potential toxicities of immunotherapy. In addition to the medical toxicities, you also have to think about the financial toxicities. Pembrolizumab is very, very expensive, and so if you don't need to give adjuvant pembrolizumab, that would also be a considerable cost saving. So I do think that's an important clinical trial to support.

The other end of the spectrum is also an area of investigation, which again, looking at that analysis of patients in KEYNOTE-522 by residual cancer burden, we knew that people who had residual cancer burdens that were higher had a quite poor prognosis. And so we do wanna know, what can we do to improve? We already knew that for people with residual disease after neoadjuvant chemotherapy, that capecitabine can be helpful. It should be noted that the CREATE-X Trial that led to the use of capecitabine in the adjuvant setting was done prior to the immunotherapy era. So we actually don't know, would capecitabine be associated with the same degree of benefit in someone who's received immunotherapy? But presumably, it should still happen because obviously capecitabine is not an immunotherapy agent, so it's a different mechanism of action. But there again, are other clinical trials looking specifically at the question of should you be doing something else besides capecitabine for people with residual disease, is there something that could do better? And so the current clinical trial that's going on is randomizing people to either sacituzumab or capecitabine after neoadjuvant chemotherapy for people with residual triple negative breast cancer after surgery and neoadjuvant chemotherapy.