COMMENTARY

To Treat and Prevent Brain Mets, Use Best Targeted Therapy Up Front

Mark G. Kris, MD

Disclosures

March 21, 2019

This transcript has been edited for clarity.

This is Dr Mark Kris from Memorial Sloan Kettering, speaking again about our understanding and management of brain metastases. I spoke earlier about the use of radiation following surgery; now we will talk about systemic therapy.

Please remember that brain metastases are devastating emotionally and physically, and they impart a much shorter survival definitely for patients with oncogene-driven cancers. Preventing them is critically important. While the data are still out there, the projected life span of people with an oncogene-driven lung cancer, at least for EGFR, is doubled if you do not have a brain metastasis.

In my ASCO (American Society of Clinical Oncology) poster this year,[1] we looked at EGFR-, HER2-, and KRAS-mutated patients. We saw an almost a 50% incidence of brain metastases and that a substantial number of people, about 15% or 20%, develop brain metastases. Preventing that would be critical for the patient's quality of life and emotional well-being.

In the November 20 issue of the Journal of Clinical Oncology (JCO), Dr Reungwetwattana[2] talked about the use of osimertinib. The beauty of osimertinib is that it is simply a better drug. It's more effective against EGFR-mutated cancers; more effective means better everywhere. Please remember that when you have an established brain metastasis, the issue is not the blood-brain barrier but the blood-tumor barrier. The blood-tumor barrier is very comparable, at least in my understanding, between the brain and elsewhere in the body. You kill the cancer in the chest, you are going to kill it in the brain. A benefit of treating with osimertinib is that the chance of developing a new brain metastasis goes down. It's a very important aspect of the drug and was conclusively shown in that paper in JCO.

That's the important message: Using a better drug treats the cancer better everywhere in the body, including the brain, and has that particular benefit of preventing progression in the brain. The take-home message is: From the start of therapy, use the best drug. For EGFR-mutant cancers, osimertinib should be the first drug we use. For ALK+ cancer, using the best drugs we have—alectinib, possibly brigatinib—up front in every patient can not only better treat the disease that is there, including in the brain, but also prevent it.

Brain metastases need to be dealt with. We need to use our best treatments to go after them if they are present, and we need to try to prevent them. Now, with better targeted therapies, we have a chance to do that. I urge you to use them and to always use them first. There is no good reason to use anything other than a third-generation tyrosine kinase inhibitor up front for EGFR and probably alectinib or brigatinib up front for ALK.

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