Shanu Modi, MD: Rena, how do you sequence T-DM1 [trastuzumab emtansine] in your HER2-positive metastatic paradigm or approach? Forgetting brain [metastases] for a moment here, is this a drug you’re still using early or something you’re reserving for later?

Rena Callahan, MD: With the presentation of the DESTINY-Breast03 trial, it changed things and moved T-DM1 out of the way. It’s difficult to know where to sequence it because we have so many great options. It’s great that T-DM1 is now there in the adjuvant setting, and it was great that it’s been there for 10 years. But now because there are better options with very strong data, at least for progression-free survival, I would favor using T-DXd [trastuzumab deruxtecan] in second-line setting. In the third-line setting because we’ve spoken so much about brain metastases, we’d generally favor using a tucatinib-based regimen. I had enrolled patients into HER2CLIMB-02 and am now enrolling into HER2CLIMB-04 to see where we can use these antibody-drug conjugates in addition to the small molecules.

But T-DM1 is being moved further back just because we have better options, unless a patient wants to avoid that toxicity, because it’s different, even if it didn’t truly show up in the trials with comparable AE [adverse events], if you’re just saying SAEs [serious adverse events] or grade 3/4 AEs. When you’re treating patients, you know that it’s different. For one, the alopecia, it’s different, and a lot of these patients have just had a good run on dual HER2 antibody therapy. Their hair has grown back. They’re living a normal life, where they look normal. Then to progress, especially if it’s small-volume progression, it’s a big deal. To move to an HNSAID [nonsteroidal anti-inflammatory drug] might cause alopecia or other types of symptoms that change how you function and how you live.

Shanu Modi, MD: I agree completely. And as these drugs are moving into the early stage setting now and the new recurrent patient we’re seeing is going to be even more different than what we’ve seen before and have had this algorithm designed for. A lot of balls are in the air here right now. But it’s good that we have these options, and we look at what’s important to the patient and what we have to offer in terms of safety profile as well as efficacy.

Transcript edited for clarity.