Treatment Options for Patients With HER2+ Breast Cancer With Brain Metastases

Alexandra S. Zimmer, MD, assistant research physician with the Women's Malignancies Branch at the National Cancer Institute, discusses treatment options for patients with HER2-positive breast cancer who have developed brain metastasis.

According to Zimmer, HER2-positive breast cancer accounts for approximately 20% of all breast cancers. Of patients with HER2-positive disease, up to 50% of them will develop brain metastasis. For patients with metastatic disease, the risk of brain metastases is higher.

Most recently, the HER2CLIMB trial (NCT02614794) found that the addition of tucatinib (Tukysa) combined with capecitabine and trastuzumab (Herceptin) can help to improve survival. Additionally, agents such as neratinib (Nerlynx) and lapatinib have shown promise, but with little clinical efficacy. The T-DM1 monoclonal antibody Trastuzumab emtansine (Kadcyla) has also shown clinical efficacy.

0:08 | HER2-positive breast cancer is around 20% of the breast cancers that we see, the numbers vary depending on where you look. And from those patients, it may be up to 50% of them develop brain metastases. Especially once they already have metastatic disease, the chances of getting brain metastases are higher, and that can go up to 50% of those cases, so very high. And then the treatments that we have available for that, specifically for HER2- positive disease, now that we know some of them have been found to be somewhat effective.

0:46 | Most recently, we had the HER2CLIMB trial that just added tucatinib combined with capecitabine and trastuzumab. That treatment was approved for second or third line in metastatic HER2-positive disease and we know there is penetration to the brain and there is some effect. And depending on the subgroup that was evaluated on the trial, the amount of benefit may vary. But in general, for the whole subgroup of patients with brain metastases, there was progression-free survival in the brain of around 9.6 months. So, it's an improvement from the previous numbers that we had, where there were five months of progression-free survival in the brain.

1:30 | There are some other agents that we know that have some penetrate period difference in the brain. T-DM1, may have some effect as well. We know that lapatinib has been demonstrated in the past to have that, neratinib has been approved for the treatment, all of them with limited effect. And what we know from preclinical data, and for evaluation translational data from this trial is that very likely the penetration is not homogeneous. I's very hard to predict how much of response you're going to have on this on this treatment. So that's the problem.