Considerations for HER2+ mBC Management: Biomarkers and Bone Disease


Fielding questions from a live audience, experts discuss the lack of biomarkers in HER2+ metastatic breast cancer and how one might address progression of bone disease.


Andrew D. Seidman, MD: We’re getting a lot of questions through the chat box. I’m going to ask 1 or 2 very quickly, and then we’ll move on to the case. Mark, one of our audience members wants to know, are there biomarkers that you are noting that may help predict benefit of antibody-drug conjugates [ADCs] in the neoadjuvant setting versus standard treatment? Anything other than HER2 expression or amplification?

Mark Pegram, MD: Yes. In the neoadjuvant setting for ADCs, probably not yet. We don’t have enough data on biomarker campaigns in that setting, particularly not with the very new ADCs like trastuzumab deruxtecan. We published a biomarker campaign on EMILIA several years ago, and we showed that high HER2transcript associated with response to T-DM1 [trastuzumab emtansine], and that’s something we’ve been showing in a number of other papers as well. Moreover, we showed that the presence or absence of a PIK3CA mutation made no difference in the case of the HER2 antibody-drug conjugate T-DM1, whereas it made a big difference in the control arm. We know the PIK3CA mutations also are a basis for resistance to trastuzumab-based chemotherapy combinations as well. Apart from those 2 kinds of unique features that we pulled out of the EMILIA experience, there is not yet a panel of biomarkers that allows you to choose one ADC over another, or an ADC versus a small molecule TKI [tyrosine kinase inhibitor] etc. We’re just not there yet. Not for lack of trying, but there are not enough data to make clinical decisions.

Andrew D. Seidman, MD: Thank you. I’m going to go to one more question, and then we’ll get to the first case. This is a question that seems like it’s a real patient for whom we’re looking for advice but it does speak to a general management issue, so I think it’s helpful. The physician writes about a patient who had trastuzumab deruxtecan as a third-line regimen, had a nice durable response in bone and visceral disease. No brain metastasis and then only progresses in bone in 2 sites. Some oligoprogression in bone. This is after a very durable response to a third-line therapy with trastuzumab deruxtecan. The question is, would you consider simply radiating the areas of bone and continuing current therapy, or is this progression and it’s time to move on and change systemic therapy? Anybody want to jump on that? Radiation to isolated sites of bone progression, continuing current therapy, or is this progression?

Mark Pegram, MD: I used to think progression was progression, but I was trained by a different generation of oncologists when I was a fellow at UCLA [University of California, Los Angeles]. The old-time oncologists would let asymptomatic, subtle progression events ride, off-study of course, and sometimes get quite a bit more mileage out of the current regimen. If they’re small, asymptomatic, etc, could you just do early interval restaging instead to follow them more closely? The answer’s probably yes, especially since it’s described that this patient had a durable PR [partial response] on trastuzumab deruxtecan. I would have no objection to following the patient more closely. Whether they need to be radiated depends on whether they’re weight-bearing, if there’s cortical involvement, etc, or pain. If not, you may not even need to radiate them. And occasionally, I’ll let some of these cases ride out and restage them in 6 weeks instead of 9 weeks.

Andrew D. Seidman, MD: Great. I’m going to try to keep us on schedule. We’ve got other questions coming in that I know we’re going to get to because I know what’s coming. Those of you who are asking questions, if I don’t shout them out right now, stay tuned because we’re going to get to them in the context of the program.

Transcript edited for clarity.

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