HER2+ Breast Cancer: Brain Metastasis Prevalence & Later-Line Therapy


Erika P. Hamilton, MD: Brain metastases are actually quite frequent in HER2+ metastatic breast cancer. Up to 50% of patients eventually will develop brain metastases, so it’s a very high unmet clinical need in the HER2+ world. We know our systemic treatments are quite effective from the neck down, but the brain does serve as a sanctuary. As we’ve gotten better at controlling HER2+ disease for more time, more people end up with brain metastases, unfortunately.

HER2+ breast cancer is 1 of the breast cancers in which brain metastases are the most frequent. Up to 50% of people ultimately will develop brain metastases in the HER2 population, so this is not a rare subgroup. Triple-negative patients also develop brain metastases. For hormonally driven breast cancer patients, it’s more infrequent.

Brain metastases universally is a very poor prognostic indicator. Patients with brain metastases often have to have brain radiation or some type of surgery to control these. The progression-free survival and, unfortunately, the overall survival of people with brain metastases are very poor when coming from a metastatic cancer. So it’s very important for us to not only control disease in the rest of the body but, also to come up with effective agents to control brain metastases as well.

We’ve seen a change in metastatic recurrence in HER2+ disease. The new statistic is that 50% of our patients with metastatic HER2+—driven breast cancer are now de novo disease, meaning they do not have early breast cancer; they just presented when they were metastatic. You kind of think, “Well, does that mean that metastatic patients are presenting later?” In fact, it doesn’t. What it actually represents is the fact that most patients we get our hands on in the early stage setting, whether that’s neoadjuvant or adjuvant, ultimately are cured. Therefore, more patients end up who are de novo.

The standard for HER2+ metastatic breast cancer in the first-line setting really is chemotherapy in combination with trastuzumab and pertuzumab or the so-called THP [docetaxel, trastuzumab, pertuzumab] regimen. Our standard second-line regimen really is T-DM1 [trastuzumab emtansine], and historically in the third-line and beyond it’s been quite open. There’s not 1 regimen that we would consider standard of care. Oftentimes these are capecitabine-containing regimens: capecitabine with the drug lapatinib or capecitabine with trastuzumab.

Patients do quite well with T-DM1 [trastuzumab emtansine] for some time. That’s traditionally our second-line regimen. Most of the time patients receive chemotherapy plus trastuzumab and pertuzumab in the first-line setting. It varies, but a lot of people receive somewhere between 6 and 8 cycles of chemotherapy in the first-line setting, and then the chemotherapy is actually dropped out. If patients are hormonally driven in addition to being HER2 driven, we often add endocrine therapy at that point, but we almost universally continue the patient on trastuzumab and pertuzumab. And a lot of patients can be on that for more than a year, sometimes years.

At the time of progression, T-DM1 [trastuzumab emtansine] has really been our standard second-line regimen. Patients do very well with this. It’s an antibody drug conjugate, so again this is chemotherapy that’s bound to the antibody to Herceptin. I liken this to the smart bomb. We infuse this into the patient’s bloodstream, and it really travels around not doing much to normal cells. When it finds its target, that HER2, the trastuzumab binds and it releases its chemotherapy right on the cell.

It’s well tolerated for patients because there’s no, what I call, naked chemotherapy there. It tends to have very low rates of nausea, lower rates of hair loss, etc. The biggest adverse effects with T-DM1 [trastuzumab emtansine] are thrombocytopenia or low platelets, and oftentimes we have to watch the liver function tests as well.

Transcript Edited for Clarity

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