Changing Treatment Paradigms in HER2+ MBC

Vijayakrishna Gadi, MD, PhD: I’m going to keep that theme going. With all the recent data and guidelines evolving, these second-line guidelines are probably going to change. There might be 2 or 3 things occupying that second line. This is a funny thing. As physicians in this field, we’ve been taught to use our best drugs first because you never know if they’re going to get that next drug because they might not be fit enough. Those data are old, and drug companies have put a lot of weight in that because they’re worried that the agent they just developed will never get used. They’re all trying to climb up the line of therapy. However, when I talk with my colleagues, we all generally believe a patient with HER2-positive metastatic breast cancer in first-line therapy will probably see the second line and will also probably see the third line. They’re all going to get these drugs, so it becomes a matter of sequencing. But we’re not fearing that patients aren’t ever going to see tucatinib or [trastuzumab] deruxtecan. They’re probably going to see them.

I’ve asked this question to a lot of colleagues in general, including community colleagues and academic colleagues, and they’re all telling me the same thing. I’m heartened to know that everybody is going to get a crack at all these things. Then it comes down to subtleties like how it’s tolerated, your quality of life, your pill burden, and all these other issues so we can maybe give our patients some of the choice back and not have to dictate, “This is what you do in the first line, second line, and third line.” There’s some discussion here, and we can make it easier for everybody. That’s my high-level thinking on this. Does that feel right to you? Are you worried that your patients aren’t going to get to the next line of therapy because they did the wrong thing in the previous line? Neil, I’ll pose that question to you.

Neil M. Iyengar, MD: Yes, I completely agree. That’s one of the positive things. We have to take the positives where we can with this disease, and one of the positive things about HER2+ breast cancer is that patients are generally seeing all of these therapies. Even as my practice is evolving with the data, I’m finding that a lot of the decisions are largely driven by the patient. If I describe the toxicity profile to a patient, they give me the directive in terms of which direction they want to go. Obviously, there are certain medical guidelines and recommendations that we can make, but when we’re talking about these gray areas, a lot of our patients can guide us in terms of treatment selection.

Vijayakrishna Gadi, MD, PhD: Mylin, this applies not just to our drugs but also how we think about radiation therapy, correct?

Mylin A. Torres, MD: Definitely. One thing that we think about a lot is a patient’s performance status in determining the number of treatments we think that they can tolerate. We have a number of options, particularly in the palliative setting or even the nonmetastatic setting. I wondered about that. When you all are thinking about the second-line treatment and beyond, is performance status a factor while choosing the regimen you’re going to recommend? Because strictly speaking, some of these clinical trials didn’t allow people with very poor performance status. How do you manage that and think about it?

Vijayakrishna Gadi, MD, PhD: Yes, I can take a crack at that. First and foremost—I’m going to pick on trastuzumab deruxtecan for a second—if the reason for the performance status is because of disease progression, then yes, I’m going to fight for them to see if they can get this molecule, because maybe I can turn the corner on that. Maybe that’s naive and cavalier, but that’s my thinking. However, if somebody is beat up from the totality of causes, whether it’s preexisting comorbidities or the cancer itself, then I’m a little worried giving a very toxic agent to somebody who may not tolerate it well and then losing enough ground enough that I don’t get to the next thing. I weigh that a little in my practice regardless of the site of the disease, whether it’s brain, liver, or lung metastases, or what have you. Neil, is that similar to what you do?

Neil M. Iyengar, MD: Yes, I agree. I think of it in the same way. I think about what it is that’s limiting their performance status. I agree with the tumor burden comment that you made, VK. If it’s their CNS [central nervous system] disease that’s limiting their performance status, that guides our treatment as well. I’d use a tucatinib-based regimen there to get CNS disease control, perhaps in addition to local therapy, to radiation if that’s an option in that setting. As we have gained more experience clinically with these drugs, even though some of our patients with not as good performance status would have been excluded from some of these trials, as Mylin importantly pointed out, there are situations where I’d feel comfortable treating folks who have a poorer performance status if I can isolate what’s contributing to it.

Transcript edited for clarity.