This week in Boston, radiation oncologists from around the world are attending the annual meeting of the American Society for Radiation Oncology (ASTRO). On Wednesday, Memorial Sloan Kettering radiation oncologist Kathryn Beal will present what she has learned treating patients at MSK with various combinations of radiation therapy and immunotherapy.
The topic of radiation and immunotherapy garnered national attention last December, when President Jimmy Carter announced he was cancer free after receiving such a combination for melanoma.
We spoke with Dr. Beal to find out more about this emerging area of medicine.
Tell us about the types of cancer you treat, and how.
I treat people with brain tumors — both primary brain tumors and also brain metastases, which are tumors that have spread from other parts of the body. Brain metastases are about ten times more common than primary brain tumors. For certain cancers, such as melanoma, non-small cell lung cancer, and even breast cancer, the incidence of brain metastases in patients with stage IV disease is quite high — in the range of 30 to 40%.
In my practice, I do a lot of stereotactic radiosurgery (SRS), in which focused beams of radiation are used to kill a tumor very precisely. I also design and deliver partial brain and whole brain radiation.
What’s been your experience with combining radiation and immunotherapy?
Once ipilimumab [a type of immune checkpoint inhibitor] was approved for melanoma, we started using it in combination with SRS for patients with melanoma that had spread to the brain. Interestingly, in about 50% of the brain metastases treated this way, we saw on follow-up imaging scans that the tumors grew to about twice their original size. We saw this in the first 11 patients and thought, Oh my gosh!
We sent these patients to the operating room because we were so concerned. But of those 11 patients, seven of them actually had no evidence of any cancer cells at all. What we saw on the scans was clearly some sort of a reactive process, perhaps related to an enhanced immune response.
We saw this same process happening in subsequent patients and so we just monitored them. By and large, most of the tumors eventually and spontaneously regressed. It was quite remarkable.
Tell us a little bit about what you’ll be presenting at ASTRO.
As we gained experience with SRS and ipilimumab, the ipi plus nivolumab combination was approved for melanoma, and then also at about the same time pembrolizumab [another drug that’s similar to nivolumab] was approved. What I’ll be presenting at ASTRO is our experience with combining pembro with SRS at MSK over the past nine months in about 20 patients. These were stage IV melanoma patients with brain metastases who received pembro at the same time as SRS, or pembro followed by SRS about a month later.
What we observed once we started doing this was that patients would come back for their first follow-up, about six to eight weeks after the radiation treatment, and they would have had a very rapid response, or even a complete response. Roughly 35% of the patients had a complete response on the first follow-up MRI and another 30% had a partial response. So about 65% either had a complete response or partial response at the first follow-up. That is really unusual. If you compare that number to patients who have SRS alone, only about 3% have a complete response or partial response on the first follow-up MRI; most of them are just stable. So this was a big change.
And the response seems to be lasting, although the follow-up is relatively short, with a median follow-up of about nine months so far. We also didn’t see any unusual toxicity with this approach.
Are you planning to test the combination of radiation and immunotherapy in other cancers?
Yes, we’re currently planning a study for patients with non-small cell lung cancer that has spread to the brain. That to me is an obvious next group to study because roughly 30 to 40% of patients with stage IV non-small cell lung cancer eventually develop brain metastases.
There is a lot of interest as well in treating primary brain tumors — specifically high-grade gliomas, or glioblastomas — with checkpoint inhibitors and radiation. There are many clinical trials looking at this now.
What’s the scientific rationale for combining radiation and immunotherapy?
Radiation is immunogenic. This means that it irritates the tumor and releases antigens, and with that you get an immune response. You see increased numbers of immune cells called T cells in the area after a dose of radiation. But then typically the natural checkpoint processes of your immune system kick in and stop that reaction. So the concept of combining a checkpoint inhibitor with radiation makes a whole lot of sense. You stop the body’s inhibition of your immune system so that you get a bigger immune reaction and allow those T cells to go to work.
Many people have credited immunotherapy, specifically pembrolizumab, for curing Jimmy Carter of cancer. Do you think the radiation he received also played a role?
Pembrolizumab does get into the brain, but I highly doubt that’s what cured Jimmy Carter’s brain metastases. It had to have been the combination, because studies have shown that patients who receive pembro alone typically do not show complete responses in their brain. So I would think his excellent response has to be attributed to the combination of radiation and pembro together. This combination can produce very dramatic responses. We show that very clearly with the data we’re presenting at ASTRO.
How has the ability to combine immunotherapy and radiation therapy changed your clinical practice?
I started specializing in brain tumors about ten years ago. When I told people that I was going to just treat brain tumors, everyone said, “Oh, that is so depressing! How can you want to do that?” But it’s remarkable how well some of our patients do now — those with metastases in particular. That’s largely due to the contribution of immunotherapy with SRS.
Historically, if you had melanoma and brain metastases, the median survival was four months. Now we have about 20% of patients who have been alive many years after their brain metastases have been treated with SRS and immunotherapy and they appear cured. I have a whole clinic full of patients who I see every three to four months. They come in to get their follow-up MRIs with me. And I tell them they look perfect. And it’s remarkable. It’s a big difference. There’s really nothing better.