Cancer Researchers Are Expanding Options for Brain Metastases

At the beginning of my career as an oncologist in the late 1980s, brain metastases were often considered an “end of the road” diagnosis. Yes, there was the rare metastases resection or whole brain radiation regimen that had a durable effect, but for the most part, the drugs used for the rest of the body just did not seem effective in the brain. In this Fall issue of CURE®, we explore transformational strategies for brain metastases — a pattern of spread we are seeing more for many tumor types as patients are living longer with metastatic cancer and we more readily use an array of brain imaging technologies when needed.

It has been known that the brain is a protected space, with a highly functional layer called the meninges that controls the passage of nutrients, among other things, and is also designed to keep toxins that might be ingested away from the delicate brain tissue. This protective layer also restricts most drugs used for cancer therapy so that only a small fraction of the concentration is seen in the brain versus the bloodstream.

In the past decade or two, we have learned much more about how drugs enter the brain and the cerebrospinal fluid, which bathes the brain and the spinal cord to which it is connected. In addition, there have been critical advancements in other key components of brain cancer treatment, which we collectively refer to as local treatment, including radiation (especially stereotactic using a focused beam), laser-based therapy and sophisticated neurosurgical techniques that minimize the complications of brain surgery so that many patients are up and walking within a day or two of surgery.

As medical treatments of breast cancer have transitioned to targeted therapies and immunotherapies and as chemotherapy has become more effective, some treatments are able to shrink brain metastases as well as tumors in other parts of the body. Many clinical trials of newer agents now permit the enrollment of patients with brain metastases to expand the number of patients who could potentially benefit and to test whether brain metastases can respond.

Some of the targeted drugs that are referred to as “small molecules” have been shown to more readily penetrate the blood-brain barrier (a network of tissue and blood vessels that keeps harmful substances from accessing the brain), making them effective for tumors that have metastasized to any organ including the brain. One recent clinical trial testing the HER2 kinase inhibitor Tukysa (tucatinib) for breast cancer showed responses in brain metastases and demonstrated that patients receiving this drug lived longer than with standard treatment. This drug is even showing effectiveness in a particularly aggressive pattern of brain metastasis known as leptomeningeal disease.

Immunotherapy used for metastatic melanoma had been found to be so effective for brain metastases that radiation is often skipped as the initial part of treatment. These encouraging trends are expected to continue as more clinical trials and innovations are dedicated to brain metastases.

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