Kinase Inhibitors Hold Promise in Treating Breast Cancer That Has Spread to the Brain

Any health issue that has to do with the brain imparts concern and fear, for good reason: This delicate, mysterious organ defines how we think and act and who we are. In many cases, patients undergo surgery and radiation without many effects on brain function, but sometimes the consequences are more pronounced, particularly in certain areas of the brain. And, of course, medically, cancer in the brain, whether from a primary tumor or disease that spreads from elsewhere, can be very serious.

The brain can be a common site of metastasis of breast cancer, depending on the biology of the disease. For example, higher-grade cancers, such as those that are triple-negative or HER2-positive, are more likely to spread to the brain.

In the case of HER2-positive disease, this may be because recent advances led to more targeted treatments. This may sound like a purely positive development because these antibody-based therapies do a better job of targeting cancer cells; however, they are large molecules and thus do not penetrate the blood-brain barrier well. That’s why, until recently, the standard of care in HER2-positive breast cancer that spread to the brain has been surgery or radiation.

In February, a combination of the chemotherapy capecitabine and Nerlynx (neratinib), a kinase inhibitor capable of crossing the blood-brain barrier, received Food and Drug Administration (FDA) approval. That was a move in the right direction, because newer drugs that inhibit the activity of proteins known as kinases are quite effective in the brain and, in some cases, may be used in place of local therapies such as surgery or radiation.

Then, in April, the FDA approved the tyrosine kinase inhibitor Tukysa (tucatinib) combined with a standard regimen, capecitabine and the monoclonal antibody Herceptin (trastuzumab), for patients with inoperable or metastatic HER2-positive breast cancer. Tukysa adds an element to the regimen that, in a clinical trial, helped slow the progress of disease that had spread to the brain and prolonged life.

Investigators are studying Tukysa plus another drug used to treat HER2-positive breast cancer, Kadcyla (T-DM1), and looking into other novel drugs expected to cross the blood-brain barrier.

Decades ago, no one would have thought that patients could live for years with brain metastases, but that is exactly what is happening. We hope to soon have even more effective drugs that can treat brain metastases from breast cancer, as is the case in melanoma, for which immunotherapy is now replacing radiation as the first option for disease that has spread to the brain.