Reflections on Future Treatment Strategies for HER2+ mBC


Experts close out their discussion on the management of HER2+ metastatic breast cancer by highlighting their hopes for future treatment strategies.


Andrew D. Seidman, MD: There are one or two great remaining questions from our audience that I’ll ask before we wrap up. This is provocative. In what type of metastatic patient does the faculty still consider a cure—it’s interesting they use the word still—as a goal and adjust management accordingly with surgery and radiation of metastatic disease? Who is the patient where you’re going to treat with the intent to cure, and how are you going to do it? Aditya, who are you treating with stage IV HER2-positive breast cancer with curative intent?

Aditya Bardia, MD, MPH:In general, for patients with metastatic stage IV disease, the intent is not cure, it’s to prolong survival and maintain improved quality of life. Having said that, if there’s a patient with oligometastatic disease, predominantly in the breast and maybe lymph node and 1 or 2 bone mets [metastases], or even 1 hepatic metastasis, I would consider standard therapy like THP [docetaxel, trastuzumab, pertuzumab]. And if the patient is doing very well 2 or 3 years into the treatment, at that time, I would consider additional therapy, be it radiation or surgery. I would say in the oligometastatic setting, maybe you can introduce the conversation of a cure.

Mark Pegram, MD:Andy, there was a nice paper presented a couple of years ago by our colleagues from Yale [Cancer Center] and MD Anderson [Cancer Center]. They did a retrospective chart review at their respective institutions and tried to identify what clinical parameters predict these exceptional responders with metastatic HER2+ disease with long remissions lasting years or decades. What they found was that patients with de novo stage IV disease who achieved a clinical CR [complete response], none of them had progression events at either of those institutions at the time of this data cut. That’s pretty provocative, so I would have a special enthusiasm for a clinical CR, and those are the patients where I’d probably go after their locoregional disease control measures with more enthusiasm compared to patients who do not achieve a clinical CR on first-line metastatic treatment.

Andrew D. Seidman, MD: Related to this subject of curing patients in durable remission, Ruta, is there a time to stop systemic therapy when you have somebody who’s in a durable CR, whether they’re on HP [trastuzumab and pertuzumab], whether they’re on an ADC [antibody-drug conjugate], whether they’re on cape [capecitabine], tucatinib, and trastuzumab? Is there a moment where enough is enough, or if it’s not broken, don’t fix it, keep treating with the same regimen?

Ruta Rao, MD:Most of us are trained to continue their current regimen until progression of disease. Butin real life sometimes these patients, especially if they are in a CR, do need a chemo [chemotherapy] holiday. We do have to take that into account and look at their quality of life, especially with drugs that are causing significant fatigue and other adverse effects.

Andrew D. Seidman, MD: Last question from the audience. Mark, I’ll aim this one at you. The question is, other than knowing that HER2 is positive, when do you use genomic testing in the treatment of HER2+ patients? Are there other genomic alterations that you think are important to know now, or that you think will be important soon? I know you’ll probably cite some examples that relate to clinical trial participation, but maybe you can speak to that at a high level. When should we be sending molecular profiling when we know that HER2 is a major target?

Mark Pegram, MD:It’s important to send genomics on patients who are considering clinical trials, first and foremost, and also patients who have exhausted all their standard HER2-targeted treatment options. In the salvage setting, that’s where you might find something that’s actionable that could lead to a clinical trial opportunity, perhaps in a basket clinical trial design, where you might uncover more rare genotypes that might have a new therapeutic that’s in clinical trials. Outside of that, I agree with you that in the routine standard of care treatment of HER2+ metastatic disease, as it stands now in 2021, there aren’t actionable gene mutations that you’re going to come across that have FDA label language that will cover that treatment off study. For the time being, HER2 trumps everything, but stay tuned, in the future that’s probably going to change.

Andrew D. Seidman, MD: We’ve seen some information on the relationship between tumor-infiltrating lymphocytes and outcomes. Are you going to tell our audience that they should be testing for PD-L1 in their patients, or is that not relevant for this population?

Mark Pegram, MD:It’s not relevant for the HER2+ population based on any data I’ve seen. It’s true that tumor-infiltrating lymphocytes is a favorable prognostic factor, but that’s true of any type of breast cancer as far as I’m aware, and that doesn’t necessarily mean you’re guaranteed a response to HER2-targeted therapy. Moreover, it certainly doesn’t guarantee lack of response to HER2-targeted therapy. There may be less of a response in patients who have sterile tumor infiltrations with no infiltrating lymphocytes, but the response rate isn’t zero in those patients either. That still needs a lot more work before that’s ready for prime time.

Andrew D. Seidman, MD: I want to thank you, Aditya, Mark, Ruta, for a lively discussion on a dynamic topic. Some people have said that we have an embarrassment of riches in HER2+ metastatic breast cancer, but we all still have patients who are succumbing from advanced HER2+ breast cancer. As much progress as we’ve made, we still have quite a way to go. We certainly have reasons for optimism, and I hope our viewing audience can sense that. We hope you found this discussion to be informative and certainly beneficial to your clinical practice. I want to thank my colleagues at CancerNetwork® for organizing this and for letting us go a little over our allotted hour. Any final thoughts from our panelists? Ruta?

Ruta Rao, MD:Just like you said, it’s exciting that we’re having new drugs and new roles for some of the drugs we’ve seen, but there’s still more work to be done. We need to keep putting our patients on these clinical trials so we can get even more options for them.

Andrew D. Seidman, MD: Closing thoughts, Mark?

Mark Pegram, MD:It was a great discussion, challenging and interesting cases, fantastic questions from our audience. I hope that our comments will be helpful to our viewers. Thank you.

Andrew D. Seidman, MD: Aditya?

Aditya Bardia, MD, MPH:I agree, a great discussion. I very much enjoyed the nuances related to management of HER2+ disease. There are a number of therapies, and the number of therapies is only going to increase. And hopefully in the future we can also focus our efforts on understanding resistance to these therapies, ADCs [antibody-drug conjugates] versus TKIs [tyrosine kinase inhibitors], because that could help with sequencing these regimens.

Andrew D. Seidman, MD: Great. Well with that, I think we’ll wrap up, and again, I want to thank you all for your attention and be well.

Transcript edited for clarity.

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