What Treatments Are Most Effective for Patients With Brain Metastases?
Dr. Langer:
So brain metastases – really, at one point, were the “bête noir” of treatment. Again, if you go back 20 years, folks diagnosed with brain metastases had extraordinarily poor survival rates. Our only treatment paradigm back then was whole-brain radiation. In the last 10 to 15 years, stereotactic radiation; very focal radiation, multiple beams all converging on separate tumors have become the standard of practice, at least when lung cancer is metastatic to the brain, specifically non-small cell.
And that has coincided with what I consider to be a revolution in how we manage folks who do develop brain metastasis. Number one, the therapies are much more focal and much more effective locally. And number two, and just as importantly, we're sparing a lot of the cognitive damage that used to occur standardly with whole-brain radiation. Whole-brain radiation's still our backup if necessary, but we try ideally to defer it or not implement it if we can.
That's part of the excitement. And at Penn, at least, we have four dedicated radiation oncologists who strictly deal with brain metastases or tumors that originate in the brain. Unfortunately, brain involvement is quite commonplace. And ironically, as patients are living longer, we're seeing more and more of this because the brain can often act as a sanctuary site. Tumors can grow in the brain, even if they're responding systemically, or what we call extracranially, outside the brain.
The other important point is that many of the targeted therapies that have developed over the last 10 to 12 years can cross the blood-brain barrier, and actually penetrate into the brain, and shrink tumors in the brain. And again, another perfect example is osimertinib, commercially known as Tagrisso. When it was compared to first-generation drugs, erlotinib (Tarceva), [inaudible 00:02:18]. Not only did it double that progression-free interval I talked about, and actually improved survival, but it had far better brain penetrance.
The incidence of newer-growing brain metastases was much lower in the group getting osimertinib, and we've seen a similar trend with ALK therapy. We have new drugs: alectinib (Alecensa), brigatinib (Alunbrig), lorlatinib (Lorbrena), all of which penetrate that blood-brain barrier far better than the forebears, the ancestral drug, crizotinib (Xalkori). So we see a four to five-fold reduction in the risk of brain progression of disease either manifesting or worsening on the brain. It's improved quality of life and it's improved survival. And frankly, the two go hand-in-hand. Longevity and quality do go hand-in-hand.
I just want to make one other point. That blood-brain barrier is really there to protect us. So if we accidentally ingest a poison, well, that big fatty membrane, that separates the brain from the rest of the body, keeps that poison from getting into the brain. Unfortunately, it also keeps many of the therapeutic agents that we use in oncology from getting into the brain. But the target therapies that I mentioned have the capacity to penetrate the blood-brain barrier, partly because they're much smaller molecules, and they can do so much more easily than antibodies or chemo. And as I said, outcomes are so much better now.
