BCC 2025 | How can ADCs de-escalate treatment in early breast cancer?
Sara Tolaney, MD, MPH, Dana Farber Cancer Institute, Boston, MA, describes how antibody-drug conjugates (ADCs) can improve treatment de-escalation in early breast cancer, noting that while ADCs offer potent chemotherapy delivery and efficacy, they still carry chemotherapy-like toxicities. De-escalation can occur by replacing a large regimen such as the one from the KEYNOTE-522 trial (NCT03036488) with a shorter treatment cycle of an ADC. However, selecting patients for de-escalation remains a challenge. This interview took place at the 2025 St. Gallen International Breast Cancer Consensus Meeting in Vienna, Austria.
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Transcript
I think one of the challenges is that ADCs still do have toxicity. So while we do get very potent delivery of chemotherapy and very robust efficacy, we do still see chemotherapy-like toxicities. Some of them cause neutropenia, alopecia, stomatitis, nausea. So I think de-escalation can occur when you replace a very large regimen, maybe with a shorter treatment cycle of an ADC. So for example, if you were to take the KEYNOTE-522 regimen, which is a lot of different drugs, and maybe if you were able to replace it with just one ADC or a short course of an ADC, maybe with the checkpoint, that would be a great improvement, certainly for patients in true de-escalation...
I think one of the challenges is that ADCs still do have toxicity. So while we do get very potent delivery of chemotherapy and very robust efficacy, we do still see chemotherapy-like toxicities. Some of them cause neutropenia, alopecia, stomatitis, nausea. So I think de-escalation can occur when you replace a very large regimen, maybe with a shorter treatment cycle of an ADC. So for example, if you were to take the KEYNOTE-522 regimen, which is a lot of different drugs, and maybe if you were able to replace it with just one ADC or a short course of an ADC, maybe with the checkpoint, that would be a great improvement, certainly for patients in true de-escalation. I think we just don’t know how to best select patients for de-escalation. And again, if we knew we could pick patients with high target expression and we could do that, that would be one thing, but we don’t, we’re not there yet. And so I think we have a ways to go to really figure out how to de-escalate therapy because we do need predictors that are going to help us narrow down who’s going to do well.
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