De-Escalation of Adjuvant Anti-HER2 Therapy and Chemo

Joyce O’Shaughnessy, MD: VK, we don’t know if we want to call it de-escalation, but personalizing the amount of treatment. People are calling it some response adapted as such. Say a little about where we are with that. What’s your take? Anything new there?

Vijayakrishna Gadi, MD: I’ve heard the same feedback. De-escalation is so 2019. In 2020 we used optimized, personalized, and there are probably better words. I get the sentiment. It feels like we’re holding something back that might be important, whereas personalization and optimization makes more sense. These response-adapted strategies are fascinating.

There was a couple presented at San Antonio Breast Cancer Symposium in non-HER2+ [human epidermal growth factor receptor 2–positive] disease this year as well. The idea that you’re letting the disease teach you which direction you go is very dynamic. What’s hard in practice is to get those strategies to a point where people are uniform and thinking about this instead of shooting from the hip. That’s going to be something we need to coalesce on—ideas on how to define these things.

For example, in recent meetings you’ve seen somebody use FDG-PET [fluorodeoxyglucose–positron emission tomography] imaging of the primary breast tumor to see if you are having a clinical response. If you’re having a clinical response, those patients might then go on to surgery right then, and if they don’t, they escalate to chemotherapy. There are a lot of trees and decision points here. At the end of the day, patients who got chemotherapy typically got the advertised pCR [pathologic complete response] rates of like 60%-plus. For patients who were randomized to the endocrine therapy plus HP [trastuzumab, pertuzumab] options up front, depending on what happens—maybe they got a pCR eventually, but that was a small group of patients. If they didn’t, then they got chemotherapy in the adjuvant setting and potentially 2 monoclonal antibodies in some of these trials for the fixed amount of time that we offer this.

It’s a little messy to look at these data and try to extract and come out with a uniformed message. When we don’t have that concretely defined for a community practitioner where breast is 1 of the many things they’re seeing, this becomes a challenging thing to memorize and to know. I don’t want to hamstring our doctors that way just yet until we have more mature data about these pathways. I agree, in principle, that if we can optimize our therapy and minimize toxicities, financial and physical toxicities, that’s very important. We’re still a little early for that outside the academic setting.

Joyce O’Shaughnessy, MD: Yeah. A lot of the response was adapted very early, before pilot feasibility trials, as opposed to randomized trials. It’s very interesting, though. People are clearly taking note of these high-level pathologic CRs and saying, “Wait a minute. What can we do a little differently?” That’s the major message.

Transcript Edited for Clarity

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