COMMENTARY

Brain Metastases: Choosing and Sequencing Local vs Systemic Therapies

Mark G. Kris, MD

Disclosures

February 15, 2019

This transcript was edited for clarity.

Hello. It's Mark Kris from Memorial Sloan Kettering, speaking about the treatment of brain metastases in patients with lung cancer, particularly those patients with oncogenic targets. Again, it's a very common and deadly problem, requiring our very close attention and optimal management of central nervous system (CNS) metastases for the benefit of our patients, in terms of symptoms and longevity.

A common issue that comes up is that we have more effective drugs for the treatment of patients with brain metastases in both the targeted therapy space and the nontargeted space. When do you give a local therapy for a brain metastasis and when do you quickly go to systemic therapy, which nowadays has a much more likely chance of benefiting the patient?

It has become a difficult issue. First, you really need a multimodality decision here. When you have a patient with a brain metastasis, all interested parties need to get together and decide what is best—is it surgery, radiation, or chemotherapy? Please include your neurologic oncologists in making these decisions.

It does a patient a disservice not to put all of our heads together at the time when a brain metastasis is suspected. Also, we need to avoid the knee-jerk reaction that the brain metastasis must be removed surgically and be given radiation and chemotherapy. I think that's not the way to go. We need a reasoned decision by all of the people who can benefit in the care of that patient.

Occasionally, surgery is the correct way to go. Very often, we don't have a diagnosis, and the brain is a site where you can get it quickly. Commonly, the tumor's location and size are such that it is to the benefit of the patient to remove it; a multimodality decision would decide that.

If the drugs work in the rest of the body, they work in the brain.

In general, what is the real risk to the patient? Yes, they suffer the consequences of a CNS metastasis. When you consider the ultimate course of the patient who has a brain metastasis, they succumb to systemic disease. First and foremost, think about how we can deliver the most effective therapy for the entire body. Nowadays, effectiveness in the rest of the body equates with effectiveness in the brain. Now that we have more effective drugs, we should consider using them upfront and keeping other modalities, including surgery and radiation, in reserve for most patients.

I asked you to look at the literature recently. There are some nice reports in the New England Journal about the use of the targeted immune checkpoint blockers in melanoma.[1] The response rates in the brain are identical to response rates in the rest of the body. If the drugs work in the rest of the body, they work in the brain. You're attacking the primary risk to the life of our patients, which is systemic spread.

I urge you to always consider adding bevacizumab for patients where it would be appropriate. Bevacizumab is a two-for-one here. Clearly, it can improve the success of the therapy—including targeted therapy, as in the case of erlotinib and bevacizumab—and systemic therapy with standard chemotherapy. In addition to improving the efficacy of the drugs, it also cuts down on CNS edema and can benefit patients symptomatically. This can also diminish the need for steroids, which is often a critical problem for these patients because they suffer from the side effects of steroids.

In terms of management, the use of dexamethasone [and other] steroids is critical. Generally, 4 mg twice a day is the standard dose. Always give Bactrim (trimethoprim/sulfamethoxazole). There's really no role for antiseizure prophylaxis except when a seizure has occurred, or in patients with a preexisting seizure disorder.

How to follow-up these patients? There are no hard and fast rules. It depends on the severity of symptoms, and again, it should be a multimodality decision. I've asked the multimodality team to decide what would be the most appropriate scanning interval for that patient.

If you start with a systemic therapy, what is the role for radiation? There is a thread in the literature, particularly in the EGFR literature, demonstrating that patients who receive radiation to the CNS in addition to targeted therapies, such as tyrosine kinase inhibitors (TKIs), have somewhat better survival. These are series, not randomized trials; however, that observation goes along with our general feeling about the treatment of oligometastases.

Importantly, if you have a patient with good systemic control on a TKI, chemotherapy, or checkpoint blocker, consider adding brain radiation when it is an isolated site or critical disease site that fits the criteria for oligometastasis. I think that is a good way of looking at it.

Again, avoid the knee-jerk saying that systemic therapy is there, it's working, and I'm not going to give radiation; and conversely, the knee-jerk is that everybody needs radiation and then systemic therapy. Think through what's right for each patient and put that multimodality team together.

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