Case 2: Relapsed HER2+ Metastatic Breast Cancer With Stable Brain Mets


The experts present and discuss a case of a patient with relapsed HER2+ metastatic breast cancer with stable brain metastases.

Joyce O’Shaughnessy, MD: Let’s go on. We have a couple of cases to talk about, brain metastasis, which is a difficult problem in our practices for many patients. Thankfully, they’re living a long time so we do need options for these patients. Bill, would you go ahead and talk to us about your case?

William Gradishar, MD: This case builds on some of the things we were talking about in patients with relapsed HER2-positive disease and brain mets [metastases]. This is the case of a 49-year-old woman who was seen by her gynecologist for her routine physical and she had a full exam, fortunately, because they detected a palpable mass in her left breast and a 3 cm node in her axilla. She was sent on for additional evaluation that included a core needle biopsy of both the mass in the breast and axilla, confirming ER-positive and HER2-positive breast cancer. She had additional imaging that showed, in addition to the palpable node, she had multiple left axillary nodes and more than one lesion in the lung itself, the largest being about 2 cm. The bone scan was negative. She had a brain MRI which was negative and they did do a lung biopsy which was concordant with what was seen in the breast; ER-positive/HER2-positive disease. She was staged as metastatic breast cancer with the presence of lung metastases.

Despite these findings, her functional status was good. She started out on a CLEOPATRA-like regimen with THP [docetaxel, trastuzumab, pertuzumab], receiving it for 6 cycles with a response and that was continued with HP [trastuzumab, pertuzumab], discontinuing the taxane. She also underwent a BSO [bilateral salpingo-oophorectomy]. She was premenopausal still at age 49 and with that they were able to start an aromatase inhibitor. Pretty remarkably she had, with both the chemotherapy, HER2-directed therapy, and treatment with optimal endocrine therapy, complete resolution of all her disease, not only in the breast, axilla but also the lung metastases. This was stable and without evidence of disease for over a year, 15 months, at which point she had reimaging done that showed now some new lung metastases, the largest of which was 1.5 cm. She was asymptomatic, but they did do brain MRI scanning and that showed three lesions, the largest of which was 1 cm.

They elected to do stereotactic radiation therapy to the brain metastases and then started her on the HER2CLIMB regimen, consisting of tucatinib, capecitabine, and trastuzumab. With that, she achieved a partial response and the CNS [central nervous system]. At 12 months she was developing new lung metastases, accompanied by symptoms of a persistent cough, and a brain MRI showed that has remained stable following the stereotactic radiation as well as the HER2CLIMB regimen. There were no new brain lesions, but there was some evidence of the residual brain metastases that were detected earlier.

Joyce O’Shaughnessy, MD: That is an, unfortunately, an all too typical case, where women present with lung metastasis, they do well, they benefit from a CLEOPATRA, and then they progress. In this particular case, Bill, you and your team got a brain MRI in this asymptomatic person, and then some subclinical small, but three met brain mets were found. How does it work in your departments, your multidisciplinary teams, of managing brain metastasis in terms of when’s the appropriate time for SRS [stereotactic radiosurgery]? Now that we have tucatinib, do we bring that into some patients? Bill, how do you transpire that she got the SRS? How does that usually work in your institution?

William Gradishar, MD: We’ve all been around long enough that we remember there weren’t neuro-oncologists back so long ago. If we saw patients with brain mets, we either managed them with something that wasn’t effective that we had available, we sent them to radiation therapy, or if there was something impending that was catastrophic, we’d bring on board the neurosurgery team. Now that it’s an engaged group where we have radiation oncology, we have neuro-oncology people who are focusing on brain disease solely, as well as the medical oncology team that has to make a decision. As a result of newer agents being available and a greater interest in CNS mets these days than in the past, this is a multidisciplinary approach.

For this patient, we had them see radiation oncology for consideration of SRS, specifically, if there was a snowstorm of disease in the brain, we would have been considering whole brain or radiation therapy. But we always engage the neuro-oncologists because they do have clinical trials that may offer the patient some other option that we don’t have available. Obviously, with some of the newer drugs that we’ve been talking about, these are at the disposal of the medical oncologists as well. But we try to have a team approach at least these days.

Joyce O’Shaughnessy, MD: How about Adam or Mark, anything about how your folks would approach a patient like this from a CNS?

Adam Brufsky, MD, PhD: I had a case a week-and-a-half ago of a woman who had recurrent disease below the neck but had what looked like a dural met with extension, maybe parenchymal, one of those things, it’s hard to tell. What we normally do when this happens is that they’re seen initially by our radiation therapist for consideration of SRS. I enrolled her in, there’s a trial now of tucatinib, trastuzumab, and deruxtecan, it’s a phase II in preparation for a phase III. She went and even though she was enrolled in the study, she was adamant that she wanted to get the radiation. The patient was nervous. It wasn’t a big lesion, about a centimeter, and she was nervous about it. This is something that’s going to come out a lot in multidisciplinary management. It turns out my colleagues in radiation therapy were unaware of the HER2CLIMB data, and so they were like: really, there’s something that actually can control brain mets systemically? It’s going to need some education of our other colleagues in multidisciplinary clinics to make them aware that there are options, systemic options that can control brain metastases prior to SRS even obviously whole brain.

Joyce O’Shaughnessy, MD: Mark, anything at Stanford in the approach you take?

Mark Pegram, MD: We have the exact experience that Bill articulated and that is we do, have a neuro-oncology clinic and tumor board. We would routinely send a referral into the neuro-oncology clinic and refer the patients there since they’ll see both neurosurgery and rad onc [radiation oncology] and med onc [medical oncology] at the same time. That’s a great venue now that there are several options and so it makes for more interesting discussions. Now that we have effective systemic therapy that gains access across the blood-brain barrier and can affect responses in the CNS, that’s a new option that’s been embraced by our tumor board participants. Oftentimes if that option presents itself, we’ll try using, for example, a tucatinib-based regimen first to see if they’ll respond to that, and that way you can delay the toxicities associated with either neurosurgery, radiation, or both.

Joyce O’Shaughnessy, MD: That’s a great place for multidisciplinary discussion these days with the expertise of neuro-oncology, we have systemic options, and what’s the right time to bring in the radiation. It’s a really great opportunity for multidisciplinary.

Transcript edited for clarity.

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