Joyce O’Shaughnessy, MD: Let's just finish by mentioning a future perspective and unmet need. Where do you hope we see the field in the next five to 10 years going? I’ll start with you there, Heather.

Heather McArthur, MD: Sure. I think that in my mind the most exciting space is whenever we see innovation, the metastatic setting, moving those strategies into the curative intent setting. And what I love to see right now is these strategies, looking at escalation strategies for patients who are at higher risk of recurrence to optimize their chance of curability, but also to optimize with de-escalation strategies for those patients who are going to have good outcomes with less therapy. And so, I think that's a really exciting area.

Joyce O’Shaughnessy, MD: I'm very excited to see some of these strategies that we've seen work so well in the metastatic setting, moving into the curative intent space. Thank you. How about you, Andrew?

Andrew Brenner, MD: Well, my bias is going to be obvious here. I want to see more CNS trials. And so, I was really, really excited to see HER2CLIMB because they included patients with active brain metastasis. I think it's a shame that we don't include more patients with active brain metastasis on these phase three trials. I think there's ways to do it, to do it safely. And I think HER2CLIMB showed that, so I'd like to see that. There are some additional ongoing studies like Destiny12B, which would be kind of more of a phase four for brain metastasis. So, we'll see what happens there. But let's get more patients on to randomized controlled trials with active CNS disease.

Joyce O’Shaughnessy, MD: How about you there, Virginia?

Virginia Kaklamani, MD: We haven't talked too much about adverse events. And we know that TDXT has a 10 to 15% incidence of interstitial lung disease, which could be fatal. We know that it can have some nausea and vomiting. We know tucatinib can have some diarrhea. So, I think it's important that we maximize our treatments, but at the same time minimize adverse events for these patients. These are patients that are going to live for a long time. And we want to improve their quality of life while treating them with active therapy. And obviously there's new agents coming out that I think we're all very excited about that hopefully will give us even more options for these patients.

Joyce O’Shaughnessy, MD: Yeah, and the TDM-1 tucatinib combination is in the adjuvant setting now, isn't it? So that's really important. But they can't benefit unless they can get it in, right? Now that one's not too terribly toxic. There's not a lot of overlapping toxicities. And TDXT is versus TDM-1. So that's just a standalone. And again, it has toxicity. You've got to get the patient through it. But I think we're particularly good at figuring out olanzapine, 2.5 milligrams at night for TDXT seems to solve the problem, et cetera.So, I think we'll get there. We'll get there for those things.

Heather McArthur, MD: Prophylaxis is really important with the trastuzumab deruxtecan.

Virginia Kaklamani, MD: We also have the atezolizumab adjuvant trial in combination with TDM-1. So, who knows, maybe we'll add immunotherapy at some point.

Joyce O’Shaughnessy, MD: That would be awesome. That would be awesome. Well, thank you guys so much. It's been really great being here with you. And thanks to Virginia Kaklamani, Andrew Brenner, and Heather McArthur, my esteemed colleagues, and for joining us all in this very lively discussion of the treatment with our patients with HER2-positive metastatic breast cancer. Thanks to CancerNetwork®️ for bringing us all together. And thank you very much, our viewing audience. I hope you found this interactive discussion useful and informative for your practice and to your patients with HER2-positive metastatic breast cancer.