Second-Line Treatment for HER2+ MBC

Vijayakrishna Gadi, MD, PhD: Should we move onto the next topic? I’m going to hand it back to Dr Torres to walk us through second-line therapies and how we think about that, what’s important, and what matters.

Mylin A. Torres, MD: Sure. We also asked the following question on Twitter: Which do you weigh most heavily when choosing a second-line therapy for a patient who has progressed on approved regimens? The choices were: A) NCCN [National Comprehensive Cancer Network] level of evidence; B) progression-free survival data; C) presence of brain metastasis; or D) mechanism of action. Neil, what are your thoughts on this?

Neil M. Iyengar, MD: We’ve touched on this a little. In the second-line setting, the responses were interesting. But for me, it’s really the patient scenario and the data. If we have a scenario like the one we just discussed where we have somebody whose CNS [central nervous system] disease is really progressing and that’s the driver of their disease, I’d be leaning toward a tucatinib [Tukysa]-based regimen because of what we saw in terms of the CNS-specific response and the overall survival in patients with active brain metastasis from the HER2CLIMB study and the follow-up data. Even as early as the second line, I’d be thinking about that regimen for somebody who has CNS disease.

If they have no CNS disease and it’s all systemic, this is where we have more of a gray area. There’s certainly a debate in the field about what we would reach for in the second line, because we have several options here. You still have the HER2CLIMB regimen, the tucatinib-based regimen, which we sometimes gloss over but has very active response systemically. That’s an option, particularly if a patient, for whatever reason, is leaning away from IV [intravenous]-based therapy and wants to stick with oral therapy. Of course, there’s the Herceptin [trastuzumab] aspect of it, but that can be given subcutaneously. That’s a discussion to be had with the patient. As you both said, the data from DESTINY-Breast03 is quite compelling in terms of even just the objective response rate for tumor shrinkage, so that’s something I’d really think about in the second-line setting.

But I do keep the bigger picture in mind. We talked a little about sequencing. If I’m thinking about second line and I have a patient who is naїve to T-DM1 [trastuzumab emtansine], that’s still a very good drug and something I’d think about in the second-line setting. Of course, that’s where the preponderance of evidence is for the use of T-DM1 in the second-line setting. The way that I think about it is: For CNS disease, I’d reach for tucatinib-based regimen in the second-line setting. For heavy burden of visceral disease and no CNS disease, I’d lean toward trastuzumab deruxtecan [Enhertu], just to tap into that objective response. If it’s middle of the road, with no CNS disease, then I still think I’d lean toward T-DM1 in the second-line setting. And if there were any contraindications from a pulmonary standpoint, such as high risk for pneumonitis, although we’re still defining what those risk factors are, I’d still be reaching toward T-DM1. That’s generally how I think about the second-line setting.

Transcript edited for clarity.