HER2+ Breast Cancer: Special Challenges and Expert Insight - Episode 2

Management Approaches for Patients with HER2+ BC at Risk for Brain Metastases

Adam M. Brufsky, MD, PhD

,
Neil M. Iyengar, MD

,
Vijayakrishna K. Gadi, MD, PhD

,
Sara A. Hurvitz, MD

An expert panel of breast oncologists discusses factors they consider when deciding whether to screen a patient with HER2+ breast cancer for brain metastases.

Adam Brufsky, MD, PhD: Let’s start with Neil with this question. If this woman comes in now, would you screen her for brain metastases? Would you do an MRI in an asymptomatic woman?

Neil Iyengar, MD: That is fascinating seeing the results come in. I wouldn’t. I am not there yet. The field is evolving. The mandatory baseline MRI in the HER2CLIMB trial has really brought this question to the forefront, but I have yet to be convinced or see convincing data that screening asymptomatic patients for brain metastases, and presumably subsequently treating those asymptomatic brain metastases early on, corresponds to improvement in survival. Without a significant amount of data, I am not routinely screening my asymptomatic patients right now. I would rechallenge with Taxol in this situation.

Adam Brufsky, MD, PhD: Either paclitaxel or docetaxel. So you would not [screen]?

Neil Iyengar, MD: I would not.

Adam Brufsky, MD, PhD: Sara, do you feel the same way as Neil?

Sara A. Hurvitz, MD: Yes, pretty much. We get lead time bias by screening more patients, we pick them up when the lesions are smaller. It’s purely hypothetical whether treating them when they are smaller earlier on actually improves long-term survival, or if it just increases the length of therapy that they’re going to get directed at the brain. I agree completely that there are no data to support that. We might have data in the future, though.

Looking at this particular patient, I would probably be referring her for the HER2CLIMB-02 trial, which is T-DM1 [trastuzumab emtansine] with or without tucatinib. Baseline brain imaging is a part of that study. As we have more agents that target the central nervous system, we might see a shift in how we treat patients. This is a second-line patient using paclitaxel or docetaxel with trastuzumab and pertuzumab, which is perfectly appropriate. But so would be moving on to T-DM1 [trastuzumab emtansine]-based therapy in this particular setting. That’s the therapy that is based on level 1 evidence from EMILIA in the second-line setting, not tucatinib-based therapy. Outside of a clinical trial, even though tucatinib is approved in the second-line setting, we don’t have phase 3 evidence that it’s better than T-DM1 [trastuzumab emtansine] in the second-line setting. I completely agree with Neil in this particular situation.

Adam Brufsky, MD, PhD: VK, I am curious. I don’t know if you remember, and other people can chime in on this. In HER2CLIMB, were there second-line patients who were allowed in the trial? I forgot how many were on, if any.

Vijayakrishna Gadi, MD PhD: I’d have to reflect on that. I believe it was phrased as “your prior lines of therapy included at some point these things.” I am sure there were some patients who had seen only T-DM1 [trastuzumab emtansine] as a metastatic patient because they relapsed or recurred within a certain time frame after pertuzumab. There may have been patients like that, and there might have been some exceptions for brain metastases. I don’t remember the details. I did have that study open, but I don’t remember the specifics.

 

Adam Brufsky, MD, PhD: Would you then screen an asymptomatic patient for brain metastases with an MRI?

Vijayakrishna Gadi, MD PhD: Sara touched on this just a moment ago. In the first page of the NCCN [National Comprehensive Cancer Network] guidelines, it says if there is a clinical trial, consider a clinical trial. That’s the perspective I start with. Interestingly enough, because of that, what happens de facto is everybody get screened at this point. It’s really those folks where there are no options, in terms of trials, in how you approach this. Right now, I am at “sometimes,” approaching “always.” I am moving up that ladder for how often I end up looking for brain metastases simply because of trials and so forth being available for patients in this context.

I chickened out on this answer, but I agree a little with Neil and Sara. But also, what’s happening day-to-day operationally is we have trials and I want people on these trials. The rechallenge is a fundamentally fascinating concept, too. In this particular patient, because she had recurred in an entirely new site, on the second appearance of new metastases in the liver, I would be a little worried that there was some type of resistance in those metastases compared to if the liver lesions had simply gotten bigger again. I know I am probably reading into the tea leaves a little on this. I would actually favor T-DM1 [trastuzumab emtansine]. It’s not that I haven’t rechallenged; I have done that. But in this context, I would probably favor T-DM1 [trastuzumab emtansine] as my next line of therapy for this patient for all the reasons I discussed.

 

Adam Brufsky, MD, PhD: Would you biopsy her liver? Maybe she is HER2-low. You don’t know.

Vijayakrishna Gadi, MD PhD: That’s a great question. As an academician, absolutely, but in the real world, I am not sure if that’s how I might practice. I do worry about loss of HER2 expression. I worry about acquisition of other mutations. Those are all things I want to know about because they could help inform me to guide the patient for her next line of therapy. Just sticking to the NCCN guidelines, if that’s all we’ve got, I don’t know how much information that adds. But if somebody is HER2-low, and I see where you’re going, are you starting to think maybe I graduate to trastuzumab deruxtecan? I might consider that in this situation in that type of circumstance.

Adam Brufsky, MD, PhD: Sara, are there any things that would make you want to do an MRI on somebody or a brain scan? I’m saying MRI, but it could obviously be CT. Is there anything clinically about a patient that would make you want to screen them if they are asymptomatic, if you do it at all?

Sara A. Hurvitz, MD: A patient’s strong desire to do so certainly influences me. It’s important for us to do shared decision-making. If I have a patient who feels adamant that they want to know, that plays a role. I have some patients who are really well-versed with the literature, and they also know other patients with HER2-positive breast cancer who’ve developed brain metastases. If they want to know and use that information to help them make treatment decisions. I’m not going to argue with them. In an asymptomatic patient, that would probably move me in that direction.

Adam Brufsky, MD, PhD: Neil, do you feel the same way?

Neil Iyengar, MD: We can all come up with one-off cases where we might do it in an asymptomatic patient. If I have a patient with vertebral metastases and maybe some epidural enhancement but no impingement in the canal, it may be an option in a discussion with the patient. But as a general rule of thumb right now, I’m not doing it.

Transcript edited for clarity.